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1
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Zheng Z, Gao J, Ma Y, Hou X. Cellular and Molecular Mechanisms of Phytochemicals Against Inflammation-Associated Diseases and Viral Infection. Cell Biol Int 2025; 49:606-633. [PMID: 40091269 DOI: 10.1002/cbin.70011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/14/2025] [Accepted: 02/18/2025] [Indexed: 03/19/2025]
Abstract
Inflammation-associated diseases have become widespread and pose a significant threat to human health, and the therapeutic methods for diverse diseases are inadequate due to the undesirable effects of synthetic ingredients. Recently, more and more evidence indicated that phytochemicals, plant secondary metabolites, have numerous therapeutic functions against human diseases via affecting a variety of mechanisms with their distinct advantages of high efficiency and low toxicity. Here, we highlight the mechanisms of phytochemicals to hinder inflammation-associated diseases (including Inflammatory diseases, cardiovascular diseases, metabolic syndrome, neurological disorders, skin diseases, respiratory diseases, kidney diseases, gastrointestinal diseases, retinal diseases, viral infections) by regulating the crosstalk among various signal cascades (including MicroRNAs, SIRT1, DNMTs, NF-κB, NLRP3, TGF-β, the Gasdermin-mediated pyroptosis pathway), which can be considered as a novel and potential therapeutic strategy. Furthermore, phytochemicals could prevent virus infection by disturbing different targets in the virus replication cycle. However, natural plants have shown limited bioavailability due to their low water solubility, the use of adjuvants such as liposomal phytochemicals, phytochemical nanoparticles and phytochemicals-phospholipid complex promote their bioavailability to exhibit beneficial effects against various diseases. The purpose of this review is to explore the molecular mechanisms and promising applications of phytochemicals in the fields of inflammation-associated diseases and virus infection to provide some direction.
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Affiliation(s)
- Zhaodi Zheng
- College of Medical Imaging and Laboratory, Jining Medical University, Jining, China
| | - Junying Gao
- Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China
| | - Yubing Ma
- College of Medical Imaging and Laboratory, Jining Medical University, Jining, China
| | - Xitan Hou
- College of Medical Imaging and Laboratory, Jining Medical University, Jining, China
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2
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Khafaga DSR, Muteeb G, Aswa DW, Aatif M, Farhan M, Allam S. Green chemistry: Modern therapies using nanocarriers for treating rare brain cancer metastasis from colon cancer. SLAS DISCOVERY : ADVANCING LIFE SCIENCES R & D 2025; 31:100213. [PMID: 39826871 DOI: 10.1016/j.slasd.2025.100213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/18/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025]
Abstract
Brain metastasis (BM) from colon cancer is associated with a poor prognosis and restricted treatment alternatives, largely due to issues related to blood-brain barrier (BBB) permeability and the negative effects of standard chemotherapy. Nanotechnology improves treatment efficacy by enabling targeted and controlled drug delivery. This review article evaluates the potential of nanotechnology-based therapies for treating colon cancer BM, emphasizing their capacity to cross the BBB, diminish metastatic growth, and enhance overall survival rates. A review of multiple studies evaluated nanoparticles (NPs) as carriers for chemotherapy, focusing on parameters including particle size, surface charge, and drug-loading capacity. The study also reviewed studies that examined BBB penetration, in vitro tumor accumulation, and in vivo tumor growth inhibition. In vitro findings indicated that NPs accumulate more efficiently in BM tissue than in healthy brain tissue and show significant BBB penetration. In vivo, nanotherapy markedly inhibited tumor growth and prolonged survival relative to conventional chemotherapy or control treatments while also exhibiting reduced side effects. Recent studies demonstrated that plant extracts can effectively and safely synthesize nanomaterials, positioning them as a viable and environmentally friendly precursor for nanomaterial production. Nanotechnology-based therapies demonstrate significant potential in the treatment of colon cancer BM by minimizing systemic toxicity, enhancing therapeutic efficacy, and facilitating more targeted drug delivery. Further research is required to confirm these findings and implement them in clinical practice.
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Affiliation(s)
- Doaa S R Khafaga
- Health Sector, Faculty of Science, Galala University, New Galala City 43511, Suez, Egypt.
| | - Ghazala Muteeb
- Department of Nursing, College of Applied Medical Sciences, King Faisal University, Al-Ahsa, Saudi Arabia.
| | - Darin W Aswa
- Faculty of Medicine, Galala University, New Galala City 43511, Suez, Egypt
| | - Mohammad Aatif
- Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Mohd Farhan
- Department of Basic Sciences, Preparatory Year, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Department of Chemistry, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia
| | - Salma Allam
- Faculty of Medicine, Galala University, New Galala City 43511, Suez, Egypt
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3
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Alshahrani S, Ashafaq M, Jali AM, Almoshari Y, Alam MI, Al Shahi H, Alshamrani AA, Hussain S. Nephrotoxic effect of cypermethrin ameliorated by nanocurcumin through antioxidative mechanism. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-03825-5. [PMID: 39878820 DOI: 10.1007/s00210-025-03825-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 01/16/2025] [Indexed: 01/31/2025]
Abstract
Cypermethrin is a pyrethroid showing nephrotoxicity by generating ROS-impaired oxidative stress and changes in inflammatory and apoptotic markers. The harmful consequences are intended to be mitigated by the imbalance between oxidants and antioxidants. The anti-inflammatory and antioxidant possessions of nanocurcumin (NC) with improved bioavailability ameliorate Cyp toxicity in rat kidneys. In our study, Group I was the control while Group II was treated alone with NC (5 mg). Group III was given 50 mg/kg of Cyp for two weeks. Groups IV, V, and VI received Cyp as in group III and co-treatment with varying NC doses after 5 days of Cyp dosing, respectively. All treatments were given orally for two weeks. After the termination of the study, LPO, 4-HNE, GSH, antioxidant catalase, and SOD were evaluated as markers of inflammation and apoptosis along with ELISA, qRT-PCR, and histopathology were used to assess morphological changes. Our work has shown that Cyp causes nephrotoxicity by altering all parameters. The Cyp-treated group was shown to have higher expression of the oxidative stress marker LPO and inflammatory interleukins as well as Bax, NF-kB, caspase-3, and caspase-9. Although LPO, inflammation, and apoptosis are reduced, antioxidant status is improved by NC.
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Affiliation(s)
- Saeed Alshahrani
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Mohammad Ashafaq
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Abdulmajeed M Jali
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Yosif Almoshari
- Department of Pharmaceutics, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Mohammad Intakhab Alam
- Department of Pharmaceutics, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Hamad Al Shahi
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Ayed A Alshamrani
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Sohail Hussain
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia.
- Gandaki Medical College, Lekhnath-27, Pokhara, Nepal.
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Sheida A, Farshadi M, Mirzaei A, Najjar Khalilabad S, Zarepour F, Taghavi SP, Hosseini Khabr MS, Ravaei F, Rafiei S, Mosadeghi K, Yazdani MS, Fakhraie A, Ghattan A, Zamani Fard MM, Shahyan M, Rafiei M, Rahimian N, Talaei Zavareh SA, Mirzaei H. Potential of Natural Products in the Treatment of Glioma: Focus on Molecular Mechanisms. Cell Biochem Biophys 2024; 82:3157-3208. [PMID: 39150676 DOI: 10.1007/s12013-024-01447-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2024] [Indexed: 08/17/2024]
Abstract
Despite the waning of traditional treatments for glioma due to possible long-term issues, the healing possibilities of substances derived from nature have been reignited in the scientific community. These natural substances, commonly found in fruits and vegetables, are considered potential alternatives to pharmaceuticals, as they have been shown in prior research to impact pathways surrounding cancer progression, metastases, invasion, and resistance. This review will explore the supposed molecular mechanisms of different natural components, such as berberine, curcumin, coffee, resveratrol, epigallocatechin-3-gallate, quercetin, tanshinone, silymarin, coumarin, and lycopene, concerning glioma treatment. While the benefits of a balanced diet containing these compounds are widely recognized, there is considerable scope for investigating the efficacy of these natural products in treating glioma.
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Affiliation(s)
- Amirhossein Sheida
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Amirhossein Mirzaei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shakiba Najjar Khalilabad
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Zarepour
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Pouya Taghavi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Sadat Hosseini Khabr
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Ravaei
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Sara Rafiei
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Kimia Mosadeghi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Sepehr Yazdani
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Fakhraie
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Ghattan
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Masoud Zamani Fard
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Shahyan
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Moein Rafiei
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Neda Rahimian
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran.
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
| | | | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Kazsoki A, Németh K, Visnovitz T, Lenzinger D, Buzás EI, Zelkó R. Formulation and characterization of nanofibrous scaffolds incorporating extracellular vesicles loaded with curcumin. Sci Rep 2024; 14:27574. [PMID: 39528605 PMCID: PMC11555084 DOI: 10.1038/s41598-024-79277-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Due to their small size, flexibility, and adhesive properties, extracellular vesicles (EVs) hold promises as effective drug delivery systems. However, challenges such as the variability in vesicle types and the need to maintain their integrity for medical applications exist. Curcumin, a compound found in turmeric and known for its diverse health benefits, including anti-cancer and anti-inflammatory properties, faces obstacles in clinical use due to issues like low solubility, limited absorption, and rapid breakdown in the body. This study aimed to incorporate large-sized curcumin-loaded extracellular vesicles (lEVs) into fast-dissolving nanofibers made of poly(vinyl alcohol) (PVA) by electrospinning. By using aqueous PVA-based solutions for electrospinning, the presence of curcumin-loaded lEVs in the nanofibers was confirmed by confocal laser scanning microscopy. Furthermore, the release study demonstrated high concentrations of the drug in nanofibers containing lEVs. These findings are significant for advancing the development and utilization of active ingredient-loaded EV systems within nanofibrous formulations, potentially leading to improved patient outcomes.
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Affiliation(s)
- Adrienn Kazsoki
- University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, Budapest, 1092, Hungary
| | - Krisztina Németh
- Department of Genetics Cell and Immunobiology, Semmelweis University, Budapest, Hungary Nagyvárad Square 4, 1089, Budapest, Hungary
- HUN-REN Translational Extracellular Vesicle Research Group, Budapest, Hungary
| | - Tamás Visnovitz
- Department of Genetics Cell and Immunobiology, Semmelweis University, Budapest, Hungary Nagyvárad Square 4, 1089, Budapest, Hungary
- Department of Plant Physiology and Molecular Plant Biology, Faculty of Science, ELTE Eötvös Loránd University, 1117, Budapest, Hungary
| | - Dorina Lenzinger
- Department of Genetics Cell and Immunobiology, Semmelweis University, Budapest, Hungary Nagyvárad Square 4, 1089, Budapest, Hungary
| | - Edit I Buzás
- Department of Genetics Cell and Immunobiology, Semmelweis University, Budapest, Hungary Nagyvárad Square 4, 1089, Budapest, Hungary
- HUN-REN Translational Extracellular Vesicle Research Group, Budapest, Hungary
- HCEMM-SU Extracellular Vesicle Research Group, Budapest, Hungary
| | - Romána Zelkó
- University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, Budapest, 1092, Hungary.
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Boroughani M, Moaveni AK, Hatami P, Mansoob Abasi N, Seyedoshohadaei SA, Pooladi A, Moradi Y, Rahimi Darehbagh R. Nanocurcumin in cancer treatment: a comprehensive systematic review. Discov Oncol 2024; 15:515. [PMID: 39349709 PMCID: PMC11442806 DOI: 10.1007/s12672-024-01272-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 08/24/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Curcumin, a compound in turmeric, shows potential in cancer treatment but is hindered by low bioavailability and solubility. Nanocurcumin, enhanced through nanotechnology, addresses these limitations, offering potential in oncological applications. This review systematically examines the efficacy, bioavailability, and safety of nanocurcumin in cancer treatment, collating data from in vitro, in vivo, and clinical studies. METHODS A comprehensive systematic search was conducted across four major databases: PubMed (Medline), Scopus, Web of Science, and Embase (up to February 2024). The selection criteria were based on the PICOT structure, and studies were assessed for risk of bias using the Cochrane bias risk tool for clinical studies and related checklists for in vitro and in vivo studies. Statistical analyses were performed in STATA software version 17. RESULTS In total, 8403 articles were identified and assessed, and then only 61 articles were found eligible to be included. Nanocurcumin formulations, especially with Poly (lactic-co-glycolic acid) (PLGA), displayed superior solubility and therapeutic efficacy. In vitro studies highlighted its enhanced cellular uptake and anti-proliferative effects, particularly against cervical cancer cells. In vivo studies confirmed its chemopreventive efficacy and potential synergy with other cancer therapies. Though in early stages, clinical trials showed promise in reducing side effects and improving efficacy in cancer treatments. CONCLUSION Nanocurcumin shows promise as an innovative approach in cancer therapy, potentially offering improved efficacy and reduced side effects compared to traditional treatments. Early clinical trials indicate its potential to enhance the quality of life for cancer patients by mitigating treatment-related toxicities and improving therapeutic outcomes. However, larger randomized controlled trials are necessary to definitively establish its clinical efficacy, optimal dosing regimens, and long-term safety profile across various cancer types. As research progresses, nanocurcumin could become a valuable addition to the oncologist's toolkit, particularly in combination therapies or for patients intolerant to conventional treatments. Future clinical studies should focus on optimizing treatment protocols, identifying responsive patient populations, and assessing long-term outcomes to facilitate the translation of these promising findings into standard clinical practice.
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Affiliation(s)
- Meshkat Boroughani
- Nanoclub Elites Association, Tehran, Iran
- Student Research Committee, Factually of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amir Kian Moaveni
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parsa Hatami
- Student Research Committee, Kurdistan University of Medical Sciences, P.O.Box: 66135-756, Sanandaj, Iran
| | - Neda Mansoob Abasi
- Student Research Committee, Kurdistan University of Medical Sciences, P.O.Box: 66135-756, Sanandaj, Iran
| | - Seyedeh Asrin Seyedoshohadaei
- Department of Psychiatry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Neurosciences Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Arash Pooladi
- Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Medical Genetics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Yousef Moradi
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Ramyar Rahimi Darehbagh
- Student Research Committee, Kurdistan University of Medical Sciences, P.O.Box: 66135-756, Sanandaj, Iran.
- Nanoclub Elites Association, Tehran, Iran.
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
- Universal Scientific Education and Research Network (USERN), Sanandaj, Kurdistan, Iran.
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Mamun MAA, Rakib A, Mandal M, Kumar S, Singla B, Singh UP. Polyphenols: Role in Modulating Immune Function and Obesity. Biomolecules 2024; 14:221. [PMID: 38397458 PMCID: PMC10887194 DOI: 10.3390/biom14020221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/02/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 75% of the world's population still use plant-based medicinal compounds, indicating the ongoing significance of phytochemicals for human health. This study emphasizes the growing body of research investigating the anti-adipogenic and anti-obesity functions of polyphenols. The functions of polyphenols, including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids, are distinct due to changes in chemical diversity and structural characteristics. This review methodically investigates the mechanisms by which naturally occurring polyphenols mediate obesity and metabolic function in immunomodulation. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role, in part, in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function and the effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required to understand the prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes a holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.
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Affiliation(s)
| | | | | | | | | | - Udai P. Singh
- Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA; (M.A.A.M.); (A.R.); (M.M.); (S.K.); (B.S.)
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8
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Zarezadeh SM, Sharafi AM, Erabi G, Tabashiri A, Teymouri N, Mehrabi H, Golzan SA, Faridzadeh A, Abdollahifar Z, Sami N, Arabpour J, Rahimi Z, Ansari A, Abbasi MR, Azizi N, Tamimi A, Poudineh M, Deravi N. Natural STAT3 Inhibitors for Cancer Treatment: A Comprehensive Literature Review. Recent Pat Anticancer Drug Discov 2024; 19:403-502. [PMID: 37534488 DOI: 10.2174/1574892818666230803100554] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 06/05/2023] [Accepted: 06/09/2023] [Indexed: 08/04/2023]
Abstract
Cancer is one of the leading causes of mortality and morbidity worldwide, affecting millions of people physically and financially every year. Over time, many anticancer treatments have been proposed and studied, including synthetic compound consumption, surgical procedures, or grueling chemotherapy. Although these treatments have improved the daily life quality of patients and increased their survival rate and life expectancy, they have also shown significant drawbacks, including staggering costs, multiple side effects, and difficulty in compliance and adherence to treatment. Therefore, natural compounds have been considered a possible key to overcoming these problems in recent years, and thorough research has been done to assess their effectiveness. In these studies, scientists have discovered a meaningful interaction between several natural materials and signal transducer and activator of transcription 3 molecules. STAT3 is a transcriptional protein that is vital for cell growth and survival. Mechanistic studies have established that activated STAT3 can increase cancer cell proliferation and invasion while reducing anticancer immunity. Thus, inhibiting STAT3 signaling by natural compounds has become one of the favorite research topics and an attractive target for developing novel cancer treatments. In the present article, we intend to comprehensively review the latest knowledge about the effects of various organic compounds on inhibiting the STAT3 signaling pathway to cure different cancer diseases.
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Affiliation(s)
- Seyed Mahdi Zarezadeh
- Students' Scientific Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Mohammad Sharafi
- Students' Scientific Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Gisou Erabi
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Arefeh Tabashiri
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Navid Teymouri
- Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hoda Mehrabi
- Student Research Committee, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Seyyed Amirhossein Golzan
- Student Research Committee, Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arezoo Faridzadeh
- Department of Immunology and Allergy, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Abdollahifar
- Student Research Committee, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Nafiseh Sami
- Student Research Committee, Tehran Medical Sciences, Islamic Azad University Medical Branch of Tehran, Tehran, Iran
| | - Javad Arabpour
- Department of Microbiology, Faculty of New Sciences, Islamic Azad University Medical Branch of Tehran, Tehran, Iran
| | - Zahra Rahimi
- School of Medicine, Zanjan University of Medical Sciences Zanjan, Iran
| | - Arina Ansari
- Student Research Committee, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | | | - Nima Azizi
- Students' Scientific Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Niloofar Deravi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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9
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Fernandes Q, Therachiyil L, Khan AQ, Bedhiafi T, Korashy HM, Bhat AA, Uddin S. Shrinking the battlefield in cancer therapy: Nanotechnology against cancer stem cells. Eur J Pharm Sci 2023; 191:106586. [PMID: 37729956 DOI: 10.1016/j.ejps.2023.106586] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 09/07/2023] [Accepted: 09/18/2023] [Indexed: 09/22/2023]
Abstract
Cancer remains one of the leading causes of mortality worldwide, presenting a significant healthcare challenge owing to the limited efficacy of current treatments. The application of nanotechnology in cancer treatment leverages the unique optical, magnetic, and electrical attributes of nanomaterials to engineer innovative, targeted therapies. Specifically, manipulating nanomaterials allows for enhanced drug loading efficiency, improved bioavailability, and targeted delivery systems, reducing the non-specific cytotoxic effects characteristic of conventional chemotherapies. Furthermore, recent advances in nanotechnology have demonstrated encouraging results in specifically targeting CSCs, a key development considering the role of these cells in disease recurrence and resistance to treatment. Despite these breakthroughs, the clinical approval rates of nano-drugs have not kept pace with research advances, pointing to existing obstacles that must be addressed. In conclusion, nanotechnology presents a novel, powerful tool in the fight against cancer, particularly in targeting the elusive and treatment-resistant CSCs. This comprehensive review delves into the intricacies of nanotherapy, explicitly targeting cancer stem cells, their markers, and associated signaling pathways.
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Affiliation(s)
- Queenie Fernandes
- College of Medicine, Qatar University, Doha, Qatar; Translational Cancer Research Facility, Hamad Medical Corporation, National Center for Cancer Care and Research, PO. Box 3050, Doha, Qatar
| | - Lubna Therachiyil
- Academic Health System, Hamad Medical Corporation, Translational Research Institute, Doha 3050, Qatar; Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar
| | - Abdul Q Khan
- Academic Health System, Hamad Medical Corporation, Translational Research Institute, Doha 3050, Qatar
| | - Takwa Bedhiafi
- Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar
| | - Hesham M Korashy
- Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar
| | - Ajaz A Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Shahab Uddin
- College of Medicine, Qatar University, Doha, Qatar; Academic Health System, Hamad Medical Corporation, Dermatology Institute, Doha 3050, Qatar; Laboratory of Animal Research Center, Qatar University, Doha 2713, Qatar; Department of Biosciences, Integral University, Lucknow, Uttar Pradesh 22602, India.
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10
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Fakhri S, Moradi SZ, Faraji F, Farhadi T, Hesami O, Iranpanah A, Webber K, Bishayee A. Current advances in nanoformulations of therapeutic agents targeting tumor microenvironment to overcome drug resistance. Cancer Metastasis Rev 2023; 42:959-1020. [PMID: 37505336 DOI: 10.1007/s10555-023-10119-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 06/13/2023] [Indexed: 07/29/2023]
Abstract
The tumor microenvironment (TME) plays a pivotal role in cancer development and progression. In this line, revealing the precise mechanisms of the TME and associated signaling pathways of tumor resistance could pave the road for cancer prevention and efficient treatment. The use of nanomedicine could be a step forward in overcoming the barriers in tumor-targeted therapy. Novel delivery systems benefit from enhanced permeability and retention effect, decreasing tumor resistance, reducing tumor hypoxia, and targeting tumor-associated factors, including immune cells, endothelial cells, and fibroblasts. Emerging evidence also indicates the engagement of multiple dysregulated mediators in the TME, such as matrix metalloproteinase, vascular endothelial growth factor, cytokines/chemokines, Wnt/β-catenin, Notch, Hedgehog, and related inflammatory and apoptotic pathways. Hence, investigating novel multitargeted agents using a novel delivery system could be a promising strategy for regulating TME and drug resistance. In recent years, small molecules from natural sources have shown favorable anticancer responses by targeting TME components. Nanoformulations of natural compounds are promising therapeutic agents in simultaneously targeting multiple dysregulated factors and mediators of TME, reducing tumor resistance mechanisms, overcoming interstitial fluid pressure and pericyte coverage, and involvement of basement membrane. The novel nanoformulations employ a vascular normalization strategy, stromal/matrix normalization, and stress alleviation mechanisms to exert higher efficacy and lower side effects. Accordingly, the nanoformulations of anticancer monoclonal antibodies and conventional chemotherapeutic agents also improved their efficacy and lessened the pharmacokinetic limitations. Additionally, the coadministration of nanoformulations of natural compounds along with conventional chemotherapeutic agents, monoclonal antibodies, and nanomedicine-based radiotherapy exhibits encouraging results. This critical review evaluates the current body of knowledge in targeting TME components by nanoformulation-based delivery systems of natural small molecules, monoclonal antibodies, conventional chemotherapeutic agents, and combination therapies in both preclinical and clinical settings. Current challenges, pitfalls, limitations, and future perspectives are also discussed.
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Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Seyed Zachariah Moradi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Farahnaz Faraji
- Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Tara Farhadi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, 6714415153, Iran
| | - Osman Hesami
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Amin Iranpanah
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Kassidy Webber
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
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11
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Insights on Dietary Polyphenols as Agents against Metabolic Disorders: Obesity as a Target Disease. Antioxidants (Basel) 2023; 12:antiox12020416. [PMID: 36829976 PMCID: PMC9952395 DOI: 10.3390/antiox12020416] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/02/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023] Open
Abstract
Obesity is a condition that leads to increased health problems associated with metabolic disorders. Synthetic drugs are available for obesity treatment, but some of these compounds have demonstrated considerable side effects that limit their use. Polyphenols are vital phytonutrients of plant origin that can be incorporated as functional food ingredients. This review presents recent developments in dietary polyphenols as anti-obesity agents. Evidence supporting the potential application of food-derived polyphenols as agents against obesity has been summarized. Literature evidence supports the effectiveness of plant polyphenols against obesity. The anti-obesity mechanisms of polyphenols have been explained by their potential to inhibit obesity-related digestive enzymes, modulate neurohormones/peptides involved in food intake, and their ability to improve the growth of beneficial gut microbes while inhibiting the proliferation of pathogenic ones. Metabolism of polyphenols by gut microbes produces different metabolites with enhanced biological properties. Thus, research demonstrates that dietary polyphenols can offer a novel path to developing functional foods for treating obesity. Upcoming investigations need to explore novel techniques, such as nanocarriers, to improve the content of polyphenols in foods and their delivery and bioavailability at the target sites in the body.
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12
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Abballe L, Spinello Z, Antonacci C, Coppola L, Miele E, Catanzaro G, Miele E. Nanoparticles for Drug and Gene Delivery in Pediatric Brain Tumors' Cancer Stem Cells: Current Knowledge and Future Perspectives. Pharmaceutics 2023; 15:pharmaceutics15020505. [PMID: 36839827 PMCID: PMC9962005 DOI: 10.3390/pharmaceutics15020505] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/24/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Primary malignant brain tumors are the most common solid neoplasm in childhood. Despite recent advances, many children affected by aggressive or metastatic brain tumors still present poor prognosis, therefore the development of more effective therapies is urgent. Cancer stem cells (CSCs) have been discovered and isolated in both pediatric and adult patients with brain tumors (e.g., medulloblastoma, gliomas and ependymoma). CSCs are a small clonal population of cancer cells responsible for brain tumor initiation, maintenance and progression, displaying resistance to conventional anticancer therapies. CSCs are characterized by a specific repertoire of surface markers and intracellular specific pathways. These unique features of CSCs biology offer the opportunity to build therapeutic approaches to specifically target these cells in the complex tumor bulk. Treatment of pediatric brain tumors with classical chemotherapeutic regimen poses challenges both for tumor location and for the presence of the blood-brain barrier (BBB). Lastly, the application of chemotherapy to a developing brain is followed by long-term sequelae, especially on cognitive abilities. Novel avenues are emerging in the therapeutic panorama taking advantage of nanomedicine. In this review we will summarize nanoparticle-based approaches and the efficacy that NPs have intrinsically demonstrated and how they are also decorated by biomolecules. Furthermore, we propose novel cargoes together with recent advances in nanoparticle design/synthesis with the final aim to specifically target the insidious CSCs population in the tumor bulk.
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Affiliation(s)
- Luana Abballe
- Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Celeste Antonacci
- Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
| | - Lucia Coppola
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Ermanno Miele
- Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0H3, UK
| | - Giuseppina Catanzaro
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
- Correspondence: (G.C.); (E.M.)
| | - Evelina Miele
- Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
- Correspondence: (G.C.); (E.M.)
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13
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MACC1-Dependent Antitumor Effect of Curcumin in Colorectal Cancer. Nutrients 2022; 14:nu14224792. [PMID: 36432477 PMCID: PMC9692505 DOI: 10.3390/nu14224792] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/07/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Metastasis is the main reason for the high mortality rate of colorectal cancer (CRC) patients. Despite the whole improvement in the field of cancer medicine, the treatment options for the patient in the late stages are very restricted. Our previous studies have elucidated metastasis-associated in colon cancer 1 (MACC1) as a direct link to metastasis formation. Therefore, we have aimed to inhibit its expression by using natural products, which are recently the center of most studies due to their low side effects and good tolerability. In this study, we have investigated the effect of one of the promising natural products, curcumin, on MACC1 expression and MACC1-induced tumor-promoting pathways. Curcumin reduced the MACC1 expression, restricted the MACC1-induced proliferation, and was able to reduce the MACC1-induced cell motility as one of the crucial steps for the distant dissemination of the tumor. We further showed the MACC1-dependent effect of curcumin on clonogenicity and wound healing. This study is, to our knowledge, the first identification of the effect of curcumin on the restriction of cancer motility, proliferation, and colony-forming ability by using MACC1 as a target.
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14
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Pourmadadi M, Abbasi P, Eshaghi MM, Bakhshi A, Ezra Manicum AL, Rahdar A, Pandey S, Jadoun S, Díez-Pascual AM. Curcumin delivery and co-delivery based on nanomaterials as an effective approach for cancer therapy. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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15
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Liao W, Li Y, Wang J, Zhao M, Chen N, Zheng Q, Wan L, Mou Y, Tang J, Wang Z. Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy. Int J Nanomedicine 2022; 17:4163-4193. [PMID: 36134202 PMCID: PMC9482958 DOI: 10.2147/ijn.s380697] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 08/25/2022] [Indexed: 11/25/2022] Open
Abstract
Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.
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Affiliation(s)
- Wenhao Liao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Yuchen Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Jing Wang
- Department of Obstetrics and Gynecology, Bishan Hospital of Traditional Chinese Medicine, Chongqing, People's Republic of China
| | - Maoyuan Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Nianzhi Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Qiao Zheng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Lina Wan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Yu Mou
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Jianyuan Tang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Zhilei Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
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16
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Pandey N, Anastasiadis P, Carney CP, Kanvinde PP, Woodworth GF, Winkles JA, Kim AJ. Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment. Adv Drug Deliv Rev 2022; 188:114415. [PMID: 35787387 PMCID: PMC10947564 DOI: 10.1016/j.addr.2022.114415] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 12/11/2022]
Abstract
Glioblastoma (GBM) is the most common malignant adult brain cancer with no curative treatment strategy. A significant hurdle in GBM treatment is effective therapeutic delivery to the brain-invading tumor cells that remain following surgery within functioning brain regions. Developing therapies that can either directly target these brain-invading tumor cells or act on other cell types and molecular processes supporting tumor cell invasion and recurrence are essential steps in advancing new treatments in the clinic. This review highlights some of the drug delivery strategies and nanotherapeutic technologies that are designed to target brain-invading GBM cells or non-neoplastic, invasion-supporting cells residing within the GBM tumor microenvironment.
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Affiliation(s)
- Nikhil Pandey
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Pavlos Anastasiadis
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Christine P Carney
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Pranjali P Kanvinde
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Graeme F Woodworth
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Fischell Department of Bioengineering, A. James Clarke School of Engineering, University of Maryland, College Park, MD, 20742, United States
| | - Jeffrey A Winkles
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
| | - Anthony J Kim
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, United States; Fischell Department of Bioengineering, A. James Clarke School of Engineering, University of Maryland, College Park, MD, 20742, United States.
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17
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Martín-Rubio P, Espiau-Romera P, Royo-García A, Caja L, Sancho P. Metabolic determinants of stemness in medulloblastoma. World J Stem Cells 2022; 14:587-598. [PMID: 36157911 PMCID: PMC9453267 DOI: 10.4252/wjsc.v14.i8.587] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/26/2022] [Accepted: 08/01/2022] [Indexed: 02/07/2023] Open
Abstract
Medulloblastomas (MBs) are the most prevalent brain tumours in children. They are classified as grade IV, the highest in malignancy, with about 30% metastatic tumours at the time of diagnosis. Cancer stem cells (CSCs) are a small subset of tumour cells that can initiate and support tumour growth. In MB, CSCs contribute to tumour initiation, metastasis, and therapy resistance. Metabolic differences among the different MB groups have started to emerge. Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways, whereas Group 3 MBs upregulate glycolysis, gluconeogenesis, glutamine anabolism, and glutathione-mediated anti-oxidant pathways. Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically. In this review, we summarise the existing knowledge about metabolic rewiring in MB, with a particular focus on MB-CSCs. Finally, we highlight some of the emerging metabolism-based therapeutic strategies for MB.
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Affiliation(s)
| | | | - Alba Royo-García
- Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza 50009, Spain
| | - Laia Caja
- Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala SE-751, Sweden
| | - Patricia Sancho
- Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza 50009, Spain
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18
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Hafez Ghoran S, Calcaterra A, Abbasi M, Taktaz F, Nieselt K, Babaei E. Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment. Molecules 2022; 27:molecules27165236. [PMID: 36014474 PMCID: PMC9414608 DOI: 10.3390/molecules27165236] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/10/2022] [Accepted: 08/13/2022] [Indexed: 02/06/2023] Open
Abstract
Throughout the United States, cancer remains the second leading cause of death. Traditional treatments induce significant medical toxic effects and unpleasant adverse reactions, making them inappropriate for long-term use. Consequently, anticancer-drug resistance and relapse are frequent in certain situations. Thus, there is an urgent necessity to find effective antitumor medications that are specific and have few adverse consequences. Curcumin is a polyphenol derivative found in the turmeric plant (Curcuma longa L.), and provides chemopreventive, antitumor, chemo-, and radio-sensitizing properties. In this paper, we summarize the new nano-based formulations of polyphenolic curcumin because of the growing interest in its application against cancers and tumors. According to recent studies, the use of nanoparticles can overcome the hydrophobic nature of curcumin, as well as improving its stability and cellular bioavailability in vitro and in vivo. Several strategies for nanocurcumin production have been developed, each with its own set of advantages and unique features. Because the majority of the curcumin-based nanoformulation evidence is still in the conceptual stage, there are still numerous issues impeding the provision of nanocurcumin as a possible therapeutic option. To support the science, further work is necessary to develop curcumin as a viable anti-cancer adjuvant. In this review, we cover the various curcumin nanoformulations and nanocurcumin implications for therapeutic uses for cancer, as well as the current state of clinical studies and patents. We further address the knowledge gaps and future research orientations required to develop curcumin as a feasible treatment candidate.
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Affiliation(s)
- Salar Hafez Ghoran
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 16666-63111, Iran
- Medicinal Plant Breeding and Development Research Institute, University of Kurdistan, Sanandaj 66177-15175, Iran
- Correspondence: (S.H.G.); or (E.B.); Tel.: +98-9144425047 (S.H.G.); Tel.: +98-4133392686 (E.B.)
| | - Andrea Calcaterra
- Department of Chemistry and Technology of Drugs, Sapienza–University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy
| | - Milad Abbasi
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 71336-54361, Iran
| | - Fatemeh Taktaz
- Department of Biology, Faculty of Sciences, University of Hakim Sabzevari, Sabzevar 96179-76487, Iran
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Kay Nieselt
- Interfaculty Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
| | - Esmaeil Babaei
- Interfaculty Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
- Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz 51666-16471, Iran
- Correspondence: (S.H.G.); or (E.B.); Tel.: +98-9144425047 (S.H.G.); Tel.: +98-4133392686 (E.B.)
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19
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Arjun P, Freeman JL, Kannan RR. Neurospecific fabrication and toxicity assessment of a PNIPAM nanogel encapsulated with trans-tephrostachin for blood-brain-barrier permeability in zebrafish model. Heliyon 2022; 8:e10237. [PMID: 36042734 PMCID: PMC9420489 DOI: 10.1016/j.heliyon.2022.e10237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 05/18/2022] [Accepted: 08/05/2022] [Indexed: 12/02/2022] Open
Abstract
Biocompatible Poly(N-isopropylacrylamide) (PNIPAM) nanogels (NGs) were developed at 40–65 nm to deliver Trans-Tephrostachin (TT) in zebrafish brain. Neurospecific PNIPAM NGs are functionalized with polysorbate 80 (PS80) to overcome the Blood Brain Barrier (BBB). The TT loaded with NG (NG + TT) was confirmed in UV-spectroscopy and transmission electron microscopy (TEM) with 90% efficiency of controlled release at 37 °C. The neurospecificity of NG was confirmed in 144 hours post fertilization (hpf) larvae with PS80 surface-treated rhodamine-B (Rh–B) conjugated NG and visualized in the zebrafish CNS. Oral gavaging of TT loaded NG with PS80 surface treatment (NG + TT + PS80) was confirmed to cross the BBB in adult zebrafish at 37 °C. TT release was detected by RP-HPLC. LC50 was determined as 250 μg/ml for NG, 172 μg/ml for NG + TT, and 0.9 μg/ml for TT at 96 hpf and confirmed the lesser toxicity in TT bound NG. Delays in growth and malformations were observed at concentrations above the 96 hpf-LC50. The behavior outcomes were varied with phase - and concentration-dependent hypo- or hyperactivity. The altered expression of genes associated with Alzheimer’s disease (AD) was found at 96 hpf of its LC50 concentration. The expression of appa was significantly increased for TT and supporting the TT to bind NG without altering the AD genes. Thus the study suggests the biocompatible potential of PNIPAM and its neurospecific delivery to the brain.
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Affiliation(s)
- Pitchai Arjun
- Neuroscience Lab, Centre for Molecular and Nanomedical Sciences (CMNS), Centre for Nanoscience and Nanotechnology (CNSNT), School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, (Deemed to Be University) Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai, 600119, Tamil Nadu, India.,School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Jennifer L Freeman
- School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Rajaretinam Rajesh Kannan
- Neuroscience Lab, Centre for Molecular and Nanomedical Sciences (CMNS), Centre for Nanoscience and Nanotechnology (CNSNT), School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, (Deemed to Be University) Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai, 600119, Tamil Nadu, India
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20
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Varnamkhasti TJ, Jafarzadeh M, Sadeghizadeh M, Aghili M. Radiosensitizing effect of dendrosomal nanoformulation of curcumin on cancer cells. Pharmacol Rep 2022; 74:718-735. [PMID: 35819593 DOI: 10.1007/s43440-022-00383-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND Curcumin was found to possess numerous pharmacological activities in clinical research, however, its biological effects together with radiation are yet to be addressed. The present study investigated whether the combined treatment of dendrosomal nanoformulation of curcumin (DNC) and gamma radiation can enhance the radiosensitivity of U87MG and MDA-MB-231 cell lines. METHODS U87MG and MDA-MB-231 cell lines were exposed to 2 Gray (Gy) and 10 μM DNC determined by MTT assay, then subjected to clonogenic assay, cell cycle assay, and flow cytometric apoptosis analysis. Acridine Orange/Ethidium Bromide (AO/EB) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) stained cells were used to study morphologic changes. The expression evaluation of putative cell cycle genes, i.e., P53, P21, CCND1, and CCNB1 was carried out by RT-qPCR. RESULTS Our findings indicated that the combined treatment with DNC and radiation might cooperatively augment the efficacy of ionizing radiation in the cancer cells and notably decrease the survival and viability of the cells in a time- and concentration-dependent manner. In addition to a synergistic effect deducted by sensitizer enhancement ratio (SER) assessment, co-treatment resulted in greater apoptotic cells than the individual treatments. Further experiments then indicated that DNC could effectively induce G2/M phase cell cycle arrest and apoptosis following irradiation. Conformably, there was a decrement of CCND1 and CCNB1 expression, and an increment of P53, P21 expression. CONCLUSIONS The data implied that DNC as a radiosensitizer can enhance the lethal effect of ionizing radiation on cancer cells which could be a promising adjuvant therapy in clinical treatments.
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Affiliation(s)
- Tahereh Jalali Varnamkhasti
- Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran
| | - Meisam Jafarzadeh
- Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran
| | - Majid Sadeghizadeh
- Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran.
| | - Mahdi Aghili
- Radiation Oncology Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, P.O. Box 13145-158, Tehran, Iran.
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21
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STAT3 in medulloblastoma: a key transcriptional regulator and potential therapeutic target. Mol Biol Rep 2022; 49:10635-10652. [PMID: 35716286 DOI: 10.1007/s11033-022-07694-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 06/08/2022] [Indexed: 10/18/2022]
Abstract
Medulloblastoma is the most common malignant brain tumor of childhood accounting for about 60% of all pediatric embryonal tumors. Despite improvements in the overall survival rate, this tumor still lacks an efficient, reliable, and less toxic therapeutic approach. Characterization of the molecular mechanisms involved in medulloblastoma initiation and progression is a crucial step for the development of effective therapies. Signal transducer and activator of transcription 3 is a convergence point for several signaling cascades that are implicated in medulloblastoma tumorigenesis. Accumulated evidence has revealed the pivotal role of signal transducer and activator of transcription 3 in medulloblastoma pathogenesis such as proliferation, survival, angiogenesis, and immunosuppression as well as maintenance, drug resistance, and recurrence. In this review, we focus on the role of signal transducer and activator of transcription 3 in medulloblastoma tumorigenesis and discuss the recent advances of signal transducer and activator of transcription 3 inhibition as a promising developed strategy for medulloblastoma therapy.
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Deng J, Wang J, Hu H, Hong J, Yang L, Zhou H, Xu D. Application of mesoporous calcium silicate nanoparticles as a potential SD carrier to improve the solubility of curcumin. J DISPER SCI TECHNOL 2022. [DOI: 10.1080/01932691.2022.2068567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Jing Deng
- National & Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass, School of Pharmacy, Changzhou University, Changzhou, P. R. China
| | - Jinwen Wang
- School of Materials Science and Engineering, Hebei University of Technology, Tianjin, P. R. China
| | - Hang Hu
- National & Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass, School of Pharmacy, Changzhou University, Changzhou, P. R. China
| | - Jun Hong
- National & Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass, School of Pharmacy, Changzhou University, Changzhou, P. R. China
| | - Lei Yang
- Center for Health Science and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, P. R. China
| | - Huan Zhou
- Center for Health Science and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, P. R. China
| | - Defeng Xu
- National & Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass, School of Pharmacy, Changzhou University, Changzhou, P. R. China
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Fuloria S, Mehta J, Chandel A, Sekar M, Rani NNIM, Begum MY, Subramaniyan V, Chidambaram K, Thangavelu L, Nordin R, Wu YS, Sathasivam KV, Lum PT, Meenakshi DU, Kumarasamy V, Azad AK, Fuloria NK. A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin. Front Pharmacol 2022; 13:820806. [PMID: 35401176 PMCID: PMC8990857 DOI: 10.3389/fphar.2022.820806] [Citation(s) in RCA: 103] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/27/2022] [Indexed: 12/16/2022] Open
Abstract
Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.
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Affiliation(s)
| | - Jyoti Mehta
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, India
| | - Aditi Chandel
- Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, India
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Malaysia
| | - Nur Najihah Izzati Mat Rani
- Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Malaysia
| | - M. Yasmin Begum
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | | | - Kumarappan Chidambaram
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Lakshmi Thangavelu
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Rusli Nordin
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, Malaysia
| | - Yuan Seng Wu
- Department of Biological Sciences and Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, Malaysia
| | | | - Pei Teng Lum
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Malaysia
| | | | - Vinoth Kumarasamy
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, Malaysia
- Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Perak, Malaysia
| | | | - Neeraj Kumar Fuloria
- Faculty of Pharmacy, AIMST University, Kedah, Malaysia
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
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Novel Repositioning Therapy for Drug-Resistant Glioblastoma: In Vivo Validation Study of Clindamycin Treatment Targeting the mTOR Pathway and Combination Therapy with Temozolomide. Cancers (Basel) 2022; 14:cancers14030770. [PMID: 35159037 PMCID: PMC8833675 DOI: 10.3390/cancers14030770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/29/2022] [Accepted: 01/30/2022] [Indexed: 02/05/2023] Open
Abstract
Simple Summary Given the significant costs and lengthy timelines of drug development and clinical trials, drug repositioning is a promising alternative to find effective treatments for brain tumors quickly and inexpensively. In the present study, using a simple drug screen of macrolides, we found that clindamycin (CLD) had cytotoxic effects on glioblastoma (GBM) cells. Further studies showed the inhibition of the mammalian target of rapamycin (mTOR) pathway as the key mechanism of action. Interestingly, we found that co-treatment with temozolomide (TMZ), the alkylating agent considered as standard therapy in GBM, enhanced these effects and proposed the inhibition of O6-methylguanine-DNA methyltransferase (MGMT) protein by CLD as a potential mechanism for this combination effect. Abstract Multimodal therapy including surgery, radiation treatment, and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to examine the signal activation patterns in GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose-dependent manner. These effects on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of the O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1)-positive cells within the tumor. These results suggest that CLD suppressed GBM cell growth by inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.
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Teja PK, Mithiya J, Kate AS, Bairwa K, Chauthe SK. Herbal nanomedicines: Recent advancements, challenges, opportunities and regulatory overview. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 96:153890. [PMID: 35026510 DOI: 10.1016/j.phymed.2021.153890] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 11/14/2021] [Accepted: 12/11/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Herbal Nano Medicines (HNMs) are nano-sized medicine containing herbal drugs as extracts, enriched fractions or biomarker constituents. HNMs have certain advantages because of their increased bioavailability and reduced toxicities. There are very few literature reports that address the common challenges of herbal nanoformulations, such as selecting the type/class of nanoformulation for an extract or a phytochemical, selection and optimisation of preparation method and physicochemical parameters. Although researchers have shown more interest in this field in the last decade, there is still an urgent need for systematic analysis of HNMs. PURPOSE This review aims to provide the recent advancement in various herbal nanomedicines like polymeric herbal nanoparticles, solid lipid nanoparticles, phytosomes, nano-micelles, self-nano emulsifying drug delivery system, nanofibers, liposomes, dendrimers, ethosomes, nanoemulsion, nanosuspension, and carbon nanotube; their evaluation parameters, challenges, and opportunities. Additionally, regulatory aspects and future perspectives of herbal nanomedicines are also being covered to some extent. METHODS The scientific data provided in this review article are retrieved by a thorough analysis of numerous research and review articles, textbooks, and patents searched using the electronic search tools like Sci-Finder, ScienceDirect, PubMed, Elsevier, Google Scholar, ACS, Medline Plus and Web of Science. RESULTS In this review, the authors suggested the suitability of nanoformulation for a particular type of extracts or enriched fraction of phytoconstituents based on their solubility and permeability profile (similar to the BCS class of drugs). This review focuses on different strategies for optimising preparation methods for various HNMs to ensure reproducibility in context with all the physicochemical parameters like particle size, surface area, zeta potential, polydispersity index, entrapment efficiency, drug loading, and drug release, along with the consistent therapeutic index. CONCLUSION A combination of herbal medicine with nanotechnology can be an essential tool for the advancement of herbal medicine research with enhanced bioavailability and fewer toxicities. Despite the challenges related to traditional medicine's safe and effective use, there is huge scope for nanotechnology-based herbal medicines. Overall, it is well stabilized that herbal nanomedicines are safer, have higher bioavailability, and have enhanced therapeutic value than conventional herbal and synthetic drugs.
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Affiliation(s)
- Parusu Kavya Teja
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Jinal Mithiya
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Abhijeet S Kate
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Khemraj Bairwa
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India..
| | - Siddheshwar K Chauthe
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India..
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Scuto M, Ontario ML, Salinaro AT, Caligiuri I, Rampulla F, Zimbone V, Modafferi S, Rizzolio F, Canzonieri V, Calabrese EJ, Calabrese V. Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology. Free Radic Biol Med 2022; 179:59-75. [PMID: 34929315 DOI: 10.1016/j.freeradbiomed.2021.12.267] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/07/2021] [Accepted: 12/16/2021] [Indexed: 12/26/2022]
Abstract
The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its "dark side" role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer.
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Affiliation(s)
- Maria Scuto
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy; Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081, Aviano, Italy
| | - Maria Laura Ontario
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy
| | - Angela Trovato Salinaro
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy.
| | - Isabella Caligiuri
- Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081, Aviano, Italy
| | - Francesco Rampulla
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy
| | - Vincenzo Zimbone
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy
| | - Sergio Modafferi
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy
| | - Flavio Rizzolio
- Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081, Aviano, Italy; Department of Molecular Sciences and Nanosystems, Ca'Foscari University of Venice, 30123, Venezia, Italy
| | - Vincenzo Canzonieri
- Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081, Aviano, Italy; Department of Medical, Surgical and Health Sciences, University of Trieste, 34127, Trieste, Italy
| | - Edward J Calabrese
- Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA, 01003, USA
| | - Vittorio Calabrese
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95124, Catania, Italy.
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27
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Tagde P, Tagde P, Tagde S, Bhattacharya T, Garg V, Akter R, Rahman MH, Najda A, Albadrani GM, Sayed AA, Akhtar MF, Saleem A, Altyar AE, Kaushik D, Abdel-Daim MM. Natural bioactive molecules: An alternative approach to the treatment and control of glioblastoma multiforme. Biomed Pharmacother 2021; 141:111928. [PMID: 34323701 DOI: 10.1016/j.biopha.2021.111928] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 07/03/2021] [Accepted: 07/12/2021] [Indexed: 12/18/2022] Open
Abstract
Glioblastoma multiforme is one of the most deadly malignant tumors, with more than 10,000 cases recorded annually in the United States. Various clinical analyses and studies show that certain chronic diseases, including cancer, interact between cell-reactive radicals rise and pathogenesis. Reactive oxygen and nitrogenous sources include endogenous (physiological processes), and exogenous sources contain reactive oxygen and nitrogen (xenobiotic interaction). The cellular oxidation/reduction shifts to oxidative stress when the regulation mechanisms of antioxidants are surpassed, and this raises the ability to damage cellular lipids, proteins, and nucleic acids. OBJECTIVE: This review is focused on how phytochemicals play crucial role against glioblastoma multiforme and to combat these, bioactive molecules and their derivatives are either used alone, in combination with anticancer drugs or as nanomedicine formulations for better cancer theranostics over the conventional approach. CONCLUSION: Bioactive molecules found in seeds, vegetables, and fruits have antioxidant, anti-inflammatory, and anticancer properties that may help cancer survivors feel better throughout chemotherapy or treatment. However, incorporating them into the nanocarrier-based drug delivery for the treatment of GBMs, which could be a promising therapeutic strategy for this tumor entity, increasing targeting effectiveness, increasing bioavailability, and reducing side effects with this target-specificity, drug internalization into cells is significantly improved, and off-target organ aggregation is reduced.
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Affiliation(s)
- Priti Tagde
- Bhabha Pharmacy Research Institute, Bhabha University, Bhopal, Madhya Pradesh, India; PRISAL Foundation (Pharmaceutical Royal International Society), India.
| | - Pooja Tagde
- Practice of Medicine Department, Govt. Homeopathy College, Bhopal, Madhya Pradesh, India
| | - Sandeep Tagde
- PRISAL Foundation (Pharmaceutical Royal International Society), India
| | - Tanima Bhattacharya
- School of Chemistry & Chemical Engineering, Hubei University, Wuhan, China; Department of Science & Engineering, Novel Global Community Educational Foundation, Australia
| | - Vishal Garg
- Jaipur School of Pharmacy, Maharaj Vinayak Global University, Jaipur, Rajasthan, India
| | - Rokeya Akter
- Department of Pharmacy, Jagannath University, Sadarghat, Dhaka 1100, Bangladesh; Department of Global Medical Science, Yonsei University Wonju College of Medicine, Yonsei University, Gangwon-do, Wonju 26426, South Korea
| | - Md Habibur Rahman
- Department of Global Medical Science, Yonsei University Wonju College of Medicine, Yonsei University, Gangwon-do, Wonju 26426, South Korea; Department of Pharmacy, Southeast University, Banani, Dhaka 1213, Bangladesh.
| | - Agnieszka Najda
- Department of Pharmacy, Southeast University, Banani, Dhaka 1213, Bangladesh.
| | - Ghadeer M Albadrani
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11474, Saudi Arabia
| | - Amany A Sayed
- Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Pakistan
| | - Ammara Saleem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Ahmed E Altyar
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia
| | - Deepak Kaushik
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, Haryana, India
| | - Mohamed M Abdel-Daim
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.
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Medeiros M, Candido MF, Valera ET, Brassesco MS. The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors? Cell Mol Life Sci 2021; 78:6161-6200. [PMID: 34333711 PMCID: PMC11072991 DOI: 10.1007/s00018-021-03906-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/20/2021] [Accepted: 07/23/2021] [Indexed: 12/16/2022]
Abstract
Despite advances in the understanding of the molecular mechanisms underlying the basic biology and pathogenesis of pediatric central nervous system (CNS) malignancies, patients still have an extremely unfavorable prognosis. Over the years, a plethora of natural and synthetic compounds has emerged for the pharmacologic intervention of the NF-kB pathway, one of the most frequently dysregulated signaling cascades in human cancer with key roles in cell growth, survival, and therapy resistance. Here, we provide a review about the state-of-the-art concerning the dysregulation of this hub transcription factor in the most prevalent pediatric CNS tumors: glioma, medulloblastoma, and ependymoma. Moreover, we compile the available literature on the anti-proliferative effects of varied NF-kB inhibitors acting alone or in combination with other therapies in vitro, in vivo, and clinical trials. As the wealth of basic research data continues to accumulate, recognizing NF-kB as a therapeutic target may provide important insights to treat these diseases, hopefully contributing to increase cure rates and lower side effects related to therapy.
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Affiliation(s)
- Mariana Medeiros
- Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Marina Ferreira Candido
- Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Elvis Terci Valera
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - María Sol Brassesco
- Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, FFCLRP-USP, University of São Paulo, Av. Bandeirantes, 3900, Bairro Monte Alegre, Ribeirão Preto, São Paulo, CEP 14040-901, Brazil.
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29
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Tian X, Fan T, Zhao W, Abbas G, Han B, Zhang K, Li N, Liu N, Liang W, Huang H, Chen W, Wang B, Xie Z. Recent advances in the development of nanomedicines for the treatment of ischemic stroke. Bioact Mater 2021; 6:2854-2869. [PMID: 33718667 PMCID: PMC7905263 DOI: 10.1016/j.bioactmat.2021.01.023] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/09/2020] [Accepted: 01/20/2021] [Indexed: 02/06/2023] Open
Abstract
Ischemic stroke is still a serious threat to human life and health, but there are few therapeutic options available to treat stroke because of limited blood-brain penetration. The development of nanotechnology may overcome some of the problems related to traditional drug development. In this review, we focus on the potential applications of nanotechnology in stroke. First, we will discuss the main molecular pathological mechanisms of ischemic stroke to develop a targeted strategy. Second, considering the important role of the blood-brain barrier in stroke treatment, we also delve mechanisms by which the blood-brain barrier protects the brain, and the reasons why the therapeutics must pass through the blood-brain barrier to achieve efficacy. Lastly, we provide a comprehensive review related to the application of nanomaterials to treat stroke, including liposomes, polymers, metal nanoparticles, carbon nanotubes, graphene, black phosphorus, hydrogels and dendrimers. To conclude, we will summarize the challenges and future prospects of nanomedicine-based stroke treatments.
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Affiliation(s)
- Xing Tian
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi, 832002, China
| | - Taojian Fan
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Wentian Zhao
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi, 832002, China
| | - Ghulam Abbas
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Bo Han
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi, 832002, China
| | - Ke Zhang
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi, 832002, China
| | - Nan Li
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Ning Liu
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Weiyuan Liang
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Hao Huang
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Wen Chen
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi, 832002, China
| | - Bing Wang
- Institute of Microscale Optoelectronics, Collaborative Innovation Centre for Optoelectronic Science & Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen Key Laboratory of Micro-Nano Photonic Information Technology, Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), Shenzhen University, Shenzhen, 518060, PR China
| | - Zhongjian Xie
- Shenzhen International Institute for Biomedical Research, 518116, Shenzhen, Guangdong, China
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30
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Patel H, Joshi J, Raval A, Shah F. Identification of Natural Compounds to Inhibit Sonic Hedgehog Pathway in Oral Cancer. Anticancer Agents Med Chem 2021; 22:905-913. [PMID: 34238174 DOI: 10.2174/1871520621666210708100747] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/21/2021] [Accepted: 05/30/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Conventional treatment resistance remains a significant problem in cancer care. Cancer stem cells might play a major role in treatment resistance, and as a result, basic stem cell pathways are instrumental in cancer. Sonic Hedgehog signaling has not been widely studied in oral cancer, and being one of the major cancer stem cell pathways, targeting it with natural compounds could open many opportunities in the treatment scenario. OBJECTIVE The objective of the study was to identify the role of various natural compounds as an anti-cancer agent for oral cancer by targeting the Hedgehog signaling pathway. METHODS The selection of natural compounds were identified through literature review and NPACT database. The protein (3M1N and 3MXW) and ligand molecules were retrieved through the PDB and PubChem database. To carry out docking experiments, the AutoDock 4.2 program was used to study the interaction between the identified protein and ligand. RESULTS Among the 13 identified natural compounds, the top three were selected based on their binding energy. The higher the binding energy on the negative side, the better the interaction formed between protein and ligand. The natural compound showing best results with 3M1N protein were Butein, Biochanin-A, and Curcumin, whereas, with 3MXW, Zerumbone, Curcumin, and Butein were identified. CONCLUSION The identified natural compounds have shown better binding energy to bind the Hh ligands in the absence/presence of a known Sonic Hedgehog inhibitor. Based on the results, natural compounds can be utilized in the current treatment modality for oral cancer either as an individual anti-cancer agent or in combination with the known Sonic Hedgehog inhibitor to curb the increasing incidence rate. Yet, in-vitro evidence in lab setup is required.
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Affiliation(s)
- Hitarth Patel
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Jigna Joshi
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Apexa Raval
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Franky Shah
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
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Nebbioso M, Franzone F, Greco A, Gharbiya M, Bonfiglio V, Polimeni A. Recent Advances and Disputes About Curcumin in Retinal Diseases. Clin Ophthalmol 2021; 15:2553-2571. [PMID: 34177257 PMCID: PMC8219301 DOI: 10.2147/opth.s306706] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 05/12/2021] [Indexed: 01/05/2023] Open
Abstract
Curcumin belongs to the group of so-called phytocompounds, biologically active molecules produced by plants exerting a beneficial effect on health. Curcumin shows a wide spectrum of different properties, being an anti-inflammatory, antioxidant, antimicrobial and antimutagenic molecule. The purpose of the review is to examine what literature reported on the characteristics of curcumin, particularly, on the beneficial and controversial aspects of this molecule, aiming for a better therapeutic management of retinal diseases. The retina is a constant target of oxidative stress, this tissue being characterized by cells rich in mitochondria and by vessels and being, obviously, continuously reached from photons affecting its layers. Particularly, the retinal ganglion cells and the photoreceptors are extremely sensitive to oxidative stress damage and it is well known that an imbalance in reactive oxygen species is often involved in several retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, central serous chorioretinopathy, macular edema, retinal ischemia-reperfusion injury, proliferative vitreoretinopathy, hereditary tapeto-retinal degenerations, and retinal and choroidal tumors. To date, several studies suggest that oral treatment with curcumin is generally well tolerated in humans and, in addition, it seems to have no negative effects: therefore, curcumin is a promising candidate as a retinal disease therapy. Unfortunately, the primary limitation of curcumin is represented by its poor bioavailability, in fact only a minimal fraction of this substance can reach the blood stream in the form of a biologically active compound. However, many steps have been made in several fields. In the future, it is expected that the strategies developed until now to allow curcumin to reach the target tissues in adequate concentrations could be ameliorated and, above all, large in vivo studies on humans are needed to demonstrate the total safety of these compounds and their effectiveness in different eye diseases.
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Affiliation(s)
- Marcella Nebbioso
- Department of Sense Organs, Sapienza University of Rome, Rome, 00185, Italy
| | - Federica Franzone
- Department of Sense Organs, Sapienza University of Rome, Rome, 00185, Italy
| | - Antonio Greco
- Department of Sense Organs, Sapienza University of Rome, Rome, 00185, Italy
| | - Magda Gharbiya
- Department of Sense Organs, Sapienza University of Rome, Rome, 00185, Italy
| | - Vincenza Bonfiglio
- Department of Experimental Biomedicine and Clinical Neuroscience, Ophthalmology Section, University of Palermo, Palermo, 90133, Italy
| | - Antonella Polimeni
- Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, Rome, 00185, Italy
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Sharma A, Panwar V, Thomas J, Chopra V, Roy HS, Ghosh D. Actin-binding carbon dots selectively target glioblastoma cells while sparing normal cells. Colloids Surf B Biointerfaces 2021; 200:111572. [PMID: 33476956 DOI: 10.1016/j.colsurfb.2021.111572] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 01/01/2021] [Accepted: 01/08/2021] [Indexed: 10/22/2022]
Abstract
Curcumin, a pleiotropic signalling molecule from Curcuma longa, is reported to be effective against multiple cancers. Despite its promising effect, curcumin had failed in clinical trials due to its low aqueous solubility, stability and poor bioavailability. While several approaches are being attempted to overcome the limitations, the improved solubility observed with curcumin-derived carbon dots appeared to be a strategy worth exploring. To assess if the carbon dots possess bio-activity similar to curcumin, we synthesized carbon dots (CurCD) from curcumin and ethylenediamine. Unlike curcumin, the as-synthesized curcumin carbon dots exhibited excellent solubility, excitation-dependent emission and photostability. The anti-cancer activity evaluated with glioblastoma cells using the well-established in vitro models indicated its comparable/enhanced activity over curcumin. Besides, the selective affinity of CurCD to the actin filament, indicated it's prospective to serve as a marker of actin filaments. In addition, the non-toxic effects observed in normal cells and fish embryos indicated CurCD was more biocompatible than curcumin. While this work reveals the superior properties of CurCD over curcumin, it provides a new approach to explore other plant derived molecules with similar limitations like curcumin.
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Affiliation(s)
- Anjana Sharma
- Institute of Nano Science and Technology, Habitat Centre, Phase 10, Mohali, 160062, Punjab, India
| | - Vineeta Panwar
- Institute of Nano Science and Technology, Habitat Centre, Phase 10, Mohali, 160062, Punjab, India
| | - Jijo Thomas
- Institute of Nano Science and Technology, Habitat Centre, Phase 10, Mohali, 160062, Punjab, India
| | - Vianni Chopra
- Institute of Nano Science and Technology, Habitat Centre, Phase 10, Mohali, 160062, Punjab, India
| | - Himadri Shekhar Roy
- Institute of Nano Science and Technology, Habitat Centre, Phase 10, Mohali, 160062, Punjab, India
| | - Deepa Ghosh
- Institute of Nano Science and Technology, Habitat Centre, Phase 10, Mohali, 160062, Punjab, India.
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Bicker J, Fortuna A, Alves G, Falcão A. Nose-to-brain Delivery of Natural Compounds for the Treatment of Central Nervous System Disorders. Curr Pharm Des 2020; 26:594-619. [PMID: 31939728 DOI: 10.2174/1381612826666200115101544] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 12/11/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Several natural compounds have demonstrated potential for the treatment of central nervous system disorders such as ischemic cerebrovascular disease, glioblastoma, neuropathic pain, neurodegenerative diseases, multiple sclerosis and migraine. This is due to their well-known antioxidant, anti-inflammatory, neuroprotective, anti-tumor, anti-ischemic and analgesic properties. Nevertheless, many of these molecules have poor aqueous solubility, low bioavailability and extensive gastrointestinal and/or hepatic first-pass metabolism, leading to a quick elimination as well as low serum and tissue concentrations. Thus, the intranasal route emerged as a viable alternative to oral or parenteral administration, by enabling a direct transport into the brain through the olfactory and trigeminal nerves. With this approach, the blood-brain barrier is circumvented and peripheral exposure is reduced, thereby minimizing possible adverse effects. OBJECTIVE Herein, brain-targeting strategies for nose-to-brain delivery of natural compounds, including flavonoids, cannabinoids, essential oils and terpenes, will be reviewed and discussed. Brain and plasma pharmacokinetics of these molecules will be analyzed and related to their physicochemical characteristics and formulation properties. CONCLUSION Natural compounds constitute relevant alternatives for the treatment of brain diseases but often require loading into nanocarrier systems to reach the central nervous system in sufficient concentrations. Future challenges lie in a deeper characterization of their therapeutic mechanisms and in the development of effective, safe and brain-targeted delivery systems for their intranasal administration.
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Affiliation(s)
- Joana Bicker
- Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.,CIBIT/ICNAS - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Ana Fortuna
- Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.,CIBIT/ICNAS - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
| | - Gilberto Alves
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilha, Portugal
| | - Amílcar Falcão
- Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.,CIBIT/ICNAS - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal
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Ryskalin L, Biagioni F, Busceti CL, Lazzeri G, Frati A, Fornai F. The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects. Molecules 2020; 25:E4839. [PMID: 33092261 PMCID: PMC7587955 DOI: 10.3390/molecules25204839] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/19/2020] [Accepted: 10/19/2020] [Indexed: 12/11/2022] Open
Abstract
The present review focuses on the multi-faceted effects of curcumin on the neurobiology glioblastoma multiforme (GBM), with a special emphasis on autophagy (ATG)-dependent molecular pathways activated by such a natural polyphenol. This is consistent with the effects of curcumin in a variety of experimental models of neurodegeneration, where the molecular events partially overlap with GBM. In fact, curcumin broadly affects various signaling pathways, which are similarly affected in cell degeneration and cell differentiation. The antitumoral effects of curcumin include growth inhibition, cell cycle arrest, anti-migration and anti-invasion, as well as chemo- and radio-sensitizing activity. Remarkably, most of these effects rely on mammalian target of rapamycin (mTOR)-dependent ATG induction. In addition, curcumin targets undifferentiated and highly tumorigenic GBM cancer stem cells (GSCs). When rescuing ATG with curcumin, the tumorigenic feature of GSCs is suppressed, thus counteracting GBM establishment and growth. It is noteworthy that targeting GSCs may also help overcome therapeutic resistance and reduce tumor relapse, which may lead to a significant improvement of GBM prognosis. The present review focuses on the multi-faceted effects of curcumin on GBM neurobiology, which represents an extension to its neuroprotective efficacy.
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Affiliation(s)
- Larisa Ryskalin
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy; (L.R.); (G.L.)
| | - Francesca Biagioni
- I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Italy; (F.B.); (C.L.B.); (A.F.)
| | - Carla L. Busceti
- I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Italy; (F.B.); (C.L.B.); (A.F.)
| | - Gloria Lazzeri
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy; (L.R.); (G.L.)
| | - Alessandro Frati
- I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Italy; (F.B.); (C.L.B.); (A.F.)
| | - Francesco Fornai
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy; (L.R.); (G.L.)
- I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, Italy; (F.B.); (C.L.B.); (A.F.)
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Sahab-Negah S, Ariakia F, Jalili-Nik M, Afshari AR, Salehi S, Samini F, Rajabzadeh G, Gorji A. Curcumin Loaded in Niosomal Nanoparticles Improved the Anti-tumor Effects of Free Curcumin on Glioblastoma Stem-like Cells: an In Vitro Study. Mol Neurobiol 2020; 57:3391-3411. [PMID: 32430842 PMCID: PMC7340659 DOI: 10.1007/s12035-020-01922-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 04/22/2020] [Indexed: 12/14/2022]
Abstract
Using a novel curcumin-loaded niosome nanoparticle (CM-NP), the present study was designed to evaluate the effect of curcumin on human glioblastoma stem-like cells (GSCs). CM-NP has a diameter of ~ 60 nm and a zeta potential of ~ - 35 mV with a constant physicochemical stability. The cytotoxic effects of free curcumin (CM) and CM-NP were investigated on GSCs obtained during the removal of a brain tumor. Both CM and CM-NP caused a dose-dependent decrease in cell proliferation and viability of GSCs. The IC50 values of CM and CM-NP on GSCs were 50 and 137 μg/ml after 24 h, respectively. CM-NP exerted significantly higher effects on GSC viability, apoptosis, cell cycle arrest, and the expression of Bax, a pro-apoptotic marker, compared with CM. In addition, the migration of GSCs was significantly impaired following the administration of CM-NP compared with CM. Furthermore, CM-NP significantly increased the values of reactive oxygen species and decreased the mRNA expressions of NF-κB and IL-6 of GSCs compared with CM. Our data also revealed that CM-NP could significantly reduce the invasiveness of GSCs compared with CM, possibly via MCP-1-mediated pathways. In addition, CM-NP exhibited a significantly greater inhibitory effect on colony formation of GSCs compared with CM. These data indicate that CM-NP exhibited stronger anti-tumor effects on GSCs than CM. Although further in vivo investigations are warranted, our results suggest that CM-NP could be an ideal carrier to deliver curcumin for potential therapeutic approaches into glioblastoma.
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Affiliation(s)
- Sajad Sahab-Negah
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
| | - Fatemeh Ariakia
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Jalili-Nik
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir R Afshari
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Sahar Salehi
- Department of Food Nanotechnology, Research Institute of Food Science and Technology, Mashhad, Iran
- Department of Materials and Metallurgical Engineering, Materials and Metallurgical Engineering Faculty, Semnan University, Semnan, Iran
| | - Fariborz Samini
- Department of Neurosurgery, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghadir Rajabzadeh
- Department of Food Nanotechnology, Research Institute of Food Science and Technology, Mashhad, Iran.
| | - Ali Gorji
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
- Department of Neurosurgery and Department of Neurology, Westfälische Wilhelms-Universität, 48149, Münster, Germany.
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, 48149, Münster, Germany.
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36
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Neuroprotection by curcumin: A review on brain delivery strategies. Int J Pharm 2020; 585:119476. [DOI: 10.1016/j.ijpharm.2020.119476] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 05/05/2020] [Accepted: 05/24/2020] [Indexed: 12/26/2022]
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Chen Y, Lu Y, Lee RJ, Xiang G. Nano Encapsulated Curcumin: And Its Potential for Biomedical Applications. Int J Nanomedicine 2020; 15:3099-3120. [PMID: 32431504 PMCID: PMC7200256 DOI: 10.2147/ijn.s210320] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 04/07/2020] [Indexed: 12/31/2022] Open
Abstract
Curcumin, a yellow-colored polyphenol extracted from the rhizome of turmeric root, is commonly used as a spice and nutritional supplement. It exhibits many pharmacological activities such as anti-inflammatory, anti-bacterial, anti-cancer, anti-Alzheimer, and anti-fungal. However, the therapeutic application of curcumin is limited by its extremely low solubility in aqueous buffer, instability in body fluids, and rapid metabolism. Nano delivery system has shown excellent potential to improve the solubility, biocompatibility and therapeutic effect of curcumin. In this review, we focus on the recent development of nano encapsulated curcumin and its potential for biomedical applications.
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Affiliation(s)
- Yan Chen
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Yao Lu
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Robert J Lee
- Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH, USA
| | - Guangya Xiang
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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Karthikeyan A, Senthil N, Min T. Nanocurcumin: A Promising Candidate for Therapeutic Applications. Front Pharmacol 2020; 11:487. [PMID: 32425772 PMCID: PMC7206872 DOI: 10.3389/fphar.2020.00487] [Citation(s) in RCA: 188] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 03/27/2020] [Indexed: 12/12/2022] Open
Abstract
Curcuma longa is an important medicinal plant and a spice in Asia. Curcumin (diferuloylmethane) is a hydrophobic bioactive ingredient found in a rhizome of the C. longa. It has drawn immense attention in recent years for its variety of biological and pharmacological action. However, its low water solubility, poor bioavailability, and rapid metabolism represent major drawbacks for its successful therapeutic applications. Hence, researchers have attempted to enhance the biological and pharmacological activity of curcumin and overcome its drawbacks by efficient delivery systems, particularly nanoencapsulation. Research efforts so far and data from the available literature have shown a satisfactory potential of nanorange formulations of curcumin (Nanocurcumin), it increases all the biological and pharmacological benefits of curcumin, which was not significantly possible earlier. For the synthesis of nanocurcumin, an array of techniques has been developed and each technique has its own advantages and individual characteristics. The two most popular and effective techniques are ionic gelation and antisolvent precipitation. So far, many curcumin nanoformulations have been developed to enhance curcumin delivery, thereby overcoming the low therapeutic effects. However, most of the nanoformulation of curcumin remained at the concept level evidence, thus, several questions and challenges still exist to recommend the nanocurcumin as a promising candidate for therapeutic applications. In this review, we discuss the different curcumin nanoformulation and nanocurcumin implications for different therapeutic applications as well as the status of ongoing clinical trials and patents. We also discuss the research gap and future research directions needed to propose curcumin as a promising therapeutic candidate.
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Affiliation(s)
- Adhimoolam Karthikeyan
- Subtropical Horticulture Research Institute, Jeju National University, Jeju, South Korea
| | - Natesan Senthil
- Department of Plant Molecular Biology and Bioinformatics, Center for Plant Molecular Biology and Biotechnology, Tamil Nadu Agricultural University, Coimbatore, India
| | - Taesun Min
- Faculty of Biotechnology, College of Applied Life Science, Sustainable Agriculture Research Institute (SARI) and Jeju International Animal Research Center (JIA), Jeju National University, Jeju, South Korea
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HSA-curcumin nanoparticles: a promising substitution for Curcumin as a Cancer chemoprevention and therapy. ACTA ACUST UNITED AC 2020; 28:209-219. [PMID: 32270402 DOI: 10.1007/s40199-020-00331-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 01/31/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Many solutions have been evaluated to deal with "chemotherapy and radiation-resistant cancer cells' as well as "severe complications of chemotherapy drugs". One of these solutions is the use of herbal compounds with antioxidant properties. Among these antioxidant compounds, curcumin is identified as the strongest one to inhibit cancerous cells proliferation. However, its clinical trials have encountered many constraints, because curcumin is insoluble in water and unstable in physiological conditions. To overcome these limitations, in this study, curcumin was conjugated with human serum albumin (HSA) and its effects on breast cancer cell lines were also measured. METHODS After making of HSA-curcumin nanoparticles (NPs) by the desolvation technique, they were characterized by the FTIR, DLS, TEM, and SEM method. At the end, its anticancer effects have been examined using MTT test and apoptosis assay. RESULTS The FTIR graph confirmed that curcumin and HSA have been conjugated along with each other. Particles size was reported to be 220 nm and 180 nm by DLS and SEM, respectively. The zeta potential of HSA-curcumin NPs was -7 mV, while it was -37 mV for curcumin. The MTT and apoptosis assay results indicated that the toxicity of HSA-curcumin NPs on the normal cell are less than curcumin; however, its anti-cancer effects on the cancer cells are much greater, compared to curcumin. CONCLUSION HSA-curcumin NPs increase curcumin solubility in water as well as its stability in physiological and acidic conditions. These factors have the ability of overwhelming the limitations on using curcumin alone, and they could result in a significant increase in the toxicity of curcumin on the cancer cells without increasing its toxicity on the normal cells. Grapical abstract.
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Shahcheraghi SH, Zangui M, Lotfi M, Ghayour-Mobarhan M, Ghorbani A, Jaliani HZ, Sadeghnia HR, Sahebkar A. Therapeutic Potential of Curcumin in the Treatment of Glioblastoma Multiforme. Curr Pharm Des 2020; 25:333-342. [PMID: 30864499 DOI: 10.2174/1381612825666190313123704] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 03/08/2019] [Indexed: 12/12/2022]
Abstract
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite standard multimodality treatment, the highly aggressive nature of GBM makes it one of the deadliest human malignancies. The anti-cancer effects of dietary phytochemicals like curcumin provide new insights to cancer treatment. Evaluation of curcumin's efficacy against different malignancies including glioblastoma has been a motivational research topic and widely studied during the recent decade. In this review, we discuss the recent observations on the potential therapeutic effects of curcumin against glioblastoma. Curcumin can target multiple signaling pathways involved in developing aggressive and drug-resistant features of glioblastoma, including pathways associated with glioma stem cell activity. Notably, combination therapy with curcumin and chemotherapeutics like temozolomide, the GBM standard therapy, as well as radiotherapy has shown synergistic response, highlighting curcumin's chemo- and radio-sensitizing effect. There are also multiple reports for curcumin nanoformulations and targeted forms showing enhanced therapeutic efficacy and passage through blood-brain barrier, as compared with natural curcumin. Furthermore, in vivo studies have revealed significant anti-tumor effects, decreased tumor size and increased survival with no notable evidence of systemic toxicity in treated animals. Finally, a pharmacokinetic study in patients with GBM has shown a detectable intratumoral concentration, thereby suggesting a potential for curcumin to exert its therapeutic effects in the brain. Despite all the evidence in support of curcumin's potential therapeutic efficacy in GBM, clinical reports are still scarce. More studies are needed to determine the effects of combination therapies with curcumin and importantly to investigate the potential for alleviating chemotherapy- and radiotherapy-induced adverse effects.
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Affiliation(s)
- Seyed Hossein Shahcheraghi
- Department of Modern Sciences & Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahtab Zangui
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Marzieh Lotfi
- Department of Medical Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medicine Sciences, Mashhad, Iran
| | - Ahmad Ghorbani
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Zarei Jaliani
- Protein Engineering Laboratory, Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hamid Reza Sadeghnia
- Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Bahmad HF, Poppiti RJ. Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets. J Clin Pathol 2020; 73:243-249. [PMID: 32034059 DOI: 10.1136/jclinpath-2019-206246] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 12/12/2019] [Accepted: 12/16/2019] [Indexed: 12/11/2022]
Abstract
Medulloblastoma (MB) is the most common malignant primary intracranial neoplasm diagnosed in childhood. Although numerous efforts have been made during the past few years to exploit novel targeted therapies for this aggressive neoplasm, there still exist substantial hitches hindering successful management of MB. Lately, progress in cancer biology has shown evidence that a subpopulation of cells within the tumour, namely cancer stem cells (CSCs), are thought to be responsible for the resistance to most chemotherapeutic agents and radiation therapy, accounting for cancer recurrence. Hence, it is crucial to identify the molecular signatures and genetic aberrations that characterise those CSCs and develop therapies that specifically target them. In this review, we aim to give an overview of the main genetic and molecular cues that depict MB-CSCs and provide a synopsis of the novel therapeutic approaches that specifically target this population of cells to attain enhanced antitumorous effects and therefore overcome resistance to therapy.
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Affiliation(s)
- Hisham F Bahmad
- Arkadi M Rywlin MD Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, Florida, USA.,Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Robert J Poppiti
- Arkadi M Rywlin MD Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, Florida, USA .,Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA
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42
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Misra R, Kandoi S, Varadaraj S, Vijayalakshmi S, Nanda A, Verma RS. Nanotheranostics: A tactic for cancer stem cells prognosis and management. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2019.101457] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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43
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Martinelli C, Pucci C, Battaglini M, Marino A, Ciofani G. Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases. Adv Healthc Mater 2020; 9:e1901589. [PMID: 31854132 DOI: 10.1002/adhm.201901589] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 11/26/2019] [Indexed: 12/11/2022]
Abstract
Many central nervous system (CNS) diseases are still incurable and only symptomatic treatments are available. Oxidative stress is suggested to be a common hallmark, being able to cause and exacerbate the neuronal cell dysfunctions at the basis of these pathologies, such as mitochondrial impairments, accumulation of misfolded proteins, cell membrane damages, and apoptosis induction. Several antioxidant compounds are tested as potential countermeasures for CNS disorders, but their efficacy is often hindered by the loss of antioxidant properties due to enzymatic degradation, low bioavailability, poor water solubility, and insufficient blood-brain barrier crossing efficiency. To overcome the limitations of antioxidant molecules, exploitation of nanostructures, either for their delivery or with inherent antioxidant properties, is proposed. In this review, after a brief discussion concerning the role of the blood-brain barrier in the CNS and the involvement of oxidative stress in some neurodegenerative diseases, the most interesting research concerning the use of nano-antioxidants is introduced and discussed, focusing on the synthesis procedures, functionalization strategies, in vitro and in vivo tests, and on recent clinical trials.
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Affiliation(s)
- Chiara Martinelli
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy
| | - Carlotta Pucci
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy
| | - Matteo Battaglini
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy
- Scuola Superiore Sant'Anna, The Biorobotics Institute, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy
| | - Attilio Marino
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy
| | - Gianni Ciofani
- Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy
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44
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Shabaninejad Z, Pourhanifeh MH, Movahedpour A, Mottaghi R, Nickdasti A, Mortezapour E, Shafiee A, Hajighadimi S, Moradizarmehri S, Sadeghian M, Mousavi SM, Mirzaei H. Therapeutic potentials of curcumin in the treatment of glioblstoma. Eur J Med Chem 2020; 188:112040. [PMID: 31927312 DOI: 10.1016/j.ejmech.2020.112040] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Revised: 01/04/2020] [Accepted: 01/04/2020] [Indexed: 02/07/2023]
Abstract
Glioblastoma multiforme (GBM), a greatly aggressive malignancy of the brain, is correlated with a poor prognosis and low rate of survival. Up to now, chemotherapy and radiation therapy after surgical approaches have been the treatments increasing the survival rates. The low efficacy of mentioned therapies as well as their side-effects has forced researchers to explore an appropriate alternative or complementary treatment for glioblastoma. In experimental models, it has been shown that curcumin has therapeutic potentials to fight against GBM. Given that curcumin has pharmacological effects against cancer stem cells, as major causes of resistance to therapy in glioblastoma cells. Moreover, it has been showed that curcumin exerts its therapeutic effects on GBM cells via affecting on apoptosis, oxidant system, and inflammatory pathways. Curcumin would possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as therapeutic agent in the treatment of GBM.
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Affiliation(s)
- Zahra Shabaninejad
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Mottaghi
- Department of Oral and Maxillofacial Surgery, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Nickdasti
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R, Iran
| | - Erfan Mortezapour
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R, Iran
| | - Alimohammad Shafiee
- Division of General Internal Medicine, Toronto General Hospital, Toronto, Canada
| | - Sarah Hajighadimi
- Division of General Internal Medicine, Toronto General Hospital, Toronto, Canada
| | - Sanaz Moradizarmehri
- Division of General Internal Medicine, Toronto General Hospital, Toronto, Canada
| | - Mohammad Sadeghian
- Orthopedic Surgeon Fellowship of Spine Surgery, Sasan General Hospital, Tehran, Iran
| | - Seyed Mojtaba Mousavi
- Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R, Iran.
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45
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Gupta PK, Dharanivasan G, Misra R, Gupta S, Verma RS. Nanomedicine in Cancer Stem Cell Therapy. Nanobiomedicine (Rij) 2020. [DOI: 10.1007/978-981-32-9898-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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46
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Pakizehkar S, Ranji N, Sohi AN, Sadeghizadeh M. Polymersome‐assisted delivery of curcumin: A suitable approach to decrease cancer stemness markers and regulate miRNAs expression in HT29 colorectal cancer cells. POLYM ADVAN TECHNOL 2019. [DOI: 10.1002/pat.4759] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Safura Pakizehkar
- Department of Biology, Faculty of Sciences, Rasht BranchIslamic Azad University Rasht Iran
| | - Najmeh Ranji
- Department of Biology, Faculty of Sciences, Rasht BranchIslamic Azad University Rasht Iran
| | | | - Majid Sadeghizadeh
- Department of Genetics, School of Biological SciencesTarbiat Modares University Tehran Iran
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47
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Gersey Z, Osiason AD, Bloom L, Shah S, Thompson JW, Bregy A, Agarwal N, Komotar RJ. Therapeutic Targeting of the Notch Pathway in Glioblastoma Multiforme. World Neurosurg 2019; 131:252-263.e2. [PMID: 31376551 DOI: 10.1016/j.wneu.2019.07.180] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 07/23/2019] [Accepted: 07/24/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND Glioblastoma (GBM) is the most common and deadly form of brain tumor. After standard treatment of resection, radiotherapy, and chemotherapy, the 5-year survival is <5%. In recent years, research has uncovered several potential targets within the Notch signaling pathway, which may lead to improved patient outcomes. METHODS A literature search was performed for articles containing the terms "Glioblastoma" and "Receptors, Notch" between 2003 and July 2015. Of the 62 articles retrieved, 46 met our criteria and were included in our review. Nine articles were identified from other sources and were subsequently included, leaving 55 articles reviewed. RESULTS Of the 55 articles reviewed, 47 used established human GBM cell lines. Seventeen articles used human GBM surgical samples. Forty-five of 48 articles that assessed Notch activity showed increased expression in GBM cell lines. Targeting the Notch pathway was carried out through Notch knockdown and overexpression and targeting δ-like ligand, Jagged, γ-secretase, ADAM10, ADAM17, and Mastermindlike protein 1. Arsenic trioxide, microRNAs, and several other compounds were shown to have an effect on the Notch pathway in GBM. Notch activity in GBM was also shown to be associated with hypoxia and certain cancer-related molecular pathways such as PI3K/AKT/mTOR and ERK/MAPK. Most articles concluded that Notch activity amplifies malignant characteristics in GBM and targeting this pathway can bring about amelioration of these effects. CONCLUSIONS Recent literature suggests targeting the Notch pathway has great potential for future therapies for GBM.
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Affiliation(s)
- Zachary Gersey
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Adam D Osiason
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Laura Bloom
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Sumedh Shah
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - John W Thompson
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Amade Bregy
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Nitin Agarwal
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Ricardo J Komotar
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
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Asghari F, Khademi R, Esmaeili Ranjbar F, Veisi Malekshahi Z, Faridi Majidi R. Application of Nanotechnology in Targeting of Cancer Stem Cells: A Review. Int J Stem Cells 2019; 12:227-239. [PMID: 31242721 PMCID: PMC6657943 DOI: 10.15283/ijsc19006] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/15/2019] [Accepted: 04/07/2019] [Indexed: 12/13/2022] Open
Abstract
Cancer is increasingly apparent as a systems-level, network happening. The central tendency of malignant alteration can be described as a two-phase procedure, where an initial increase of network plasticity is followed by reducing plasticity at late stages of tumor improvement. Cancer stem cells (CSCs) are cancer cells that take characteristics associated with normal stem cells. Cancer therapy has been based on the concept that most of the cancer cells have a similar ability to separate metastasise and kill the host. In this review, we addressed the use of nanotechnology in the treatment of cancer stem cells.
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Affiliation(s)
- Fatemeh Asghari
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Rahele Khademi
- International affairs, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Esmaeili Ranjbar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ziba Veisi Malekshahi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Faridi Majidi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Lübtow MM, Nelke LC, Seifert J, Kühnemundt J, Sahay G, Dandekar G, Nietzer SL, Luxenhofer R. Drug induced micellization into ultra-high capacity and stable curcumin nanoformulations: Physico-chemical characterization and evaluation in 2D and 3D in vitro models. J Control Release 2019; 303:162-180. [DOI: 10.1016/j.jconrel.2019.04.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/04/2019] [Accepted: 04/10/2019] [Indexed: 01/02/2023]
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50
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Taniguchi H, Suzuki Y, Natori Y. The Evolving Landscape of Cancer Stem Cells and Ways to Overcome Cancer Heterogeneity. Cancers (Basel) 2019; 11:cancers11040532. [PMID: 31013960 PMCID: PMC6520864 DOI: 10.3390/cancers11040532] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 04/02/2019] [Accepted: 04/04/2019] [Indexed: 12/18/2022] Open
Abstract
Cancer stem cells (CSCs) with therapeutic resistance and plasticity can be found in various types of tumors and are recognized as attractive targets for treatments. As CSCs are derived from tissue stem or progenitor cells, and/or dedifferentiated mature cells, their signal transduction pathways are critical in the regulation of CSCs; chronic inflammation causes the accumulation of genetic mutations and aberrant epigenetic changes in these cells, potentially leading to the production of CSCs. However, the nature of CSCs appears to be stronger than the treatments of the past. To improve the treatments targeting CSCs, it is important to inhibit several molecules on the signaling cascades in CSCs simultaneously, and to overcome cancer heterogeneity caused by the plasticity. To select suitable target molecules for CSCs, we have to explore the landscape of CSCs from the perspective of cancer stemness and signaling systems, based on the curated databases of cancer-related genes. We have been studying the integration of a broad range of knowledge and experiences from cancer biology, and also from other interdisciplinary basic sciences. In this review, we have introduced the concept of developing novel strategies targeting CSCs.
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Affiliation(s)
- Hiroaki Taniguchi
- The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-0071, Japan.
- Clinical and Translational Research Center Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
| | - Yasunori Suzuki
- Clinical and Translational Research Center Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
| | - Yukikazu Natori
- BioThinkTank Co. Ltd. 4-10-1-E1706 Minatomirai, Nishi-ku Yokohama, Kanagawa 220-0012, Japan.
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