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Meena UK, Maurya AK. Bacopa monnieri Extract Diminish Hypoxia-Induced Anxiety by Regulating HIF-1α Signaling and Enhancing the Antioxidant Defense System in Hippocampus. Neuromolecular Med 2025; 27:11. [PMID: 39853472 DOI: 10.1007/s12017-025-08833-5] [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] [Received: 10/26/2024] [Accepted: 01/10/2025] [Indexed: 01/26/2025]
Abstract
Hypoxia is a significant stressor, and stabilized hypoxia-inducible factor-1α (HIF-1α) regulates the expression of numerous genes, leading to various biochemical, molecular, physiological and genomic changes. The body's oxygen-sensing system activates gene expression to protect brain tissues from hypoxia. Gamma-aminobutyric acid, an inhibitory neurotransmitter, regulates brain excitability during hypoxia through the activation of HIF-1 α. Herbal medicines have been widely used for managing various toxicological effects and disorders including hypoxia; however, the data on safety, efficacy and the molecular mechanisms that increase vulnerability or lethality against hypoxia are still lacking and urgently need to be investigated. The Current study aims to investigate how Bacopa monnieri extract (BME), specially CDRI-08 affects the hippocampus of mice subjected to conditions that simulate hypoxia. The pre and co-treatment of mice involved administrating BME (200 mg/kg BW) for 14 days, followed by exposure to CoCl2 (40 mg/kg BW). BME decreased the levels of reactive oxygen species (ROS) and lipid peroxidation, while it increased the Gamma-aminobutyric acid receptor subunit-ɑ1 (GABAAR-ɑ1) level as well as the activity of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Furthermore BME reduced the levels of HIF-1α and its downstream targets glucose transporter-1 (GLUT-1) and erythropoietin (EPO) in the DG, CA1, and CA3 regions of hippocampus. Additionally, results obtained from the open field, elevated zero maze and plus maze tests indicate that BME restores anxiety caused by hypoxia. Together, these findings suggested that BME mitigates the harmful effects of oxidative stress and altered hypoxia related signaling in hippocampus; and may provide a basis for its therapeutic use in the recovery from hypoxia-led anxiety.
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Affiliation(s)
- Upendra Kumar Meena
- Biochemistry and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221 005, India
| | - Akhilendra Kumar Maurya
- Biochemistry and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.
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Kaur C, Sahu SK, Bansal K, DeLiberto LK, Zhang J, Tewari D, Bishayee A. Targeting Peroxisome Proliferator-Activated Receptor-β/δ, Reactive Oxygen Species and Redox Signaling with Phytocompounds for Cancer Therapy. Antioxid Redox Signal 2024; 41:342-395. [PMID: 38299535 DOI: 10.1089/ars.2023.0442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
Significance: Peroxisome proliferator-activated receptors (PPARs) have a moderately preserved amino-terminal domain, an extremely preserved DNA-binding domain, an integral hinge region, and a distinct ligand-binding domain that are frequently encountered with the other nuclear receptors. PPAR-β/δ is among the three nuclear receptor superfamily members in the PPAR group. Recent Advances: Emerging studies provide an insight on natural compounds that have gained increasing attention as potential anticancer agents due to their ability to target multiple pathways involved in cancer development and progression. Critical Issues: Modulation of PPAR-β/δ activity has been suggested as a potential therapeutic strategy for cancer management. This review focuses on the ability of bioactive phytocompounds to impact reactive oxygen species (ROS) and redox signaling by targeting PPAR-β/δ for cancer therapy. The rise of ROS in cancer cells may play an important part in the initiation and progression of cancer. However, excessive levels of ROS stress can also be toxic to the cells and cancer cells with increased oxidative stress are likely to be more vulnerable to damage by further ROS insults induced by exogenous agents, such as phytocompounds and therapeutic agents. Therefore, redox modulation is a way to selectively kill cancer cells without causing significant toxicity to normal cells. However, use of antioxidants together with cancer drugs may risk the effect of treatment as both act through opposite mechanisms. Future Directions: It is advisable to employ more thorough and detailed methodologies to undertake mechanistic explorations of numerous phytocompounds. Moreover, conducting additional clinical studies is recommended to establish optimal dosages, efficacy, and the impact of different phytochemicals on PPAR-β/δ.
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Affiliation(s)
- Charanjit Kaur
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India
| | - Sanjeev Kumar Sahu
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India
| | - Keshav Bansal
- Department of Pharmaceutics, Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Lindsay K DeLiberto
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Jie Zhang
- College of Food Science and Engineering, Jilin University, Changchun, China
| | - Devesh Tewari
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
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Cecerska-Heryć E, Wiśniewska Z, Serwin N, Polikowska A, Goszka M, Engwert W, Michałów J, Pękała M, Budkowska M, Michalczyk A, Dołęgowska B. Can Compounds of Natural Origin Be Important in Chemoprevention? Anticancer Properties of Quercetin, Resveratrol, and Curcumin-A Comprehensive Review. Int J Mol Sci 2024; 25:4505. [PMID: 38674092 PMCID: PMC11050349 DOI: 10.3390/ijms25084505] [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] [Received: 02/15/2024] [Revised: 04/17/2024] [Accepted: 04/18/2024] [Indexed: 04/28/2024] Open
Abstract
Malignant tumors are the second most common cause of death worldwide. More attention is being paid to the link between the body's impaired oxidoreductive balance and cancer incidence. Much attention is being paid to polyphenols derived from plants, as one of their properties is an antioxidant character: the ability to eliminate reactive oxygen and nitrogen species, chelate specific metal ions, modulate signaling pathways affecting inflammation, and raise the level and activity of antioxidant enzymes while lowering those with oxidative effects. The following three compounds, resveratrol, quercetin, and curcumin, are polyphenols modulating multiple molecular targets, or increasing pro-apoptotic protein expression levels and decreasing anti-apoptotic protein expression levels. Experiments conducted in vitro and in vivo on animals and humans suggest using them as chemopreventive agents based on antioxidant properties. The advantage of these natural polyphenols is low toxicity and weak adverse effects at higher doses. However, the compounds discussed are characterized by low bioavailability and solubility, which may make achieving the blood concentrations needed for the desired effect challenging. The solution may lie in derivatives of naturally occurring polyphenols subjected to structural modifications that enhance their beneficial effects or work on implementing new ways of delivering antioxidants that improve their solubility and bioavailability.
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Affiliation(s)
- Elżbieta Cecerska-Heryć
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Zofia Wiśniewska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Natalia Serwin
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Aleksandra Polikowska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Małgorzata Goszka
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Weronika Engwert
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Jaśmina Michałów
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Maja Pękała
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
| | - Marta Budkowska
- Department of Medical Analytics, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Anna Michalczyk
- Department of Psychiatry, Pomeranian Medical University of Szczecin, Broniewskiego 26, 71-460 Szczecin, Poland;
| | - Barbara Dołęgowska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland; (Z.W.); (N.S.); (A.P.); (M.G.); (W.E.); (J.M.); (M.P.); (B.D.)
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Zhong J, Zong S, Wang J, Feng M, Wang J, Zhang H, Xiong L. Role of neutrophils on cancer cells and other immune cells in the tumor microenvironment. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119493. [PMID: 37201766 DOI: 10.1016/j.bbamcr.2023.119493] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/25/2023] [Accepted: 05/09/2023] [Indexed: 05/20/2023]
Abstract
The notion that neutrophils only perform a specific set of single functions in the body has changed with the advancement of research methods. As the most abundant myeloid cells in human blood, neutrophils are currently emerging as important regulators of cancer. Given the duality of neutrophils, neutrophil-based tumor therapy has been clinically carried out in recent years and has made some progress. But due to the complexity of the tumor microenvironment, the therapeutic effect is still not satisfactory. Therefore, in this review, we discuss the direct interaction of neutrophils with the five most common cancer cells and other immune cells in the tumor microenvironment. Also, this review covered current limitations, potential future possibilities, and therapeutic approaches targeting neutrophil function in cancer therapy.
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Affiliation(s)
- Junpei Zhong
- Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China
| | - Siwen Zong
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Jiayang Wang
- First Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Mingrui Feng
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Jie Wang
- Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Medical College, Fujian province university, Xiamen 361023, China
| | - Hongyan Zhang
- Department of Burn, The First Affiliated Hospital, Nanchang University, Nanchang 330066, China.
| | - Lixia Xiong
- Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China; Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Medical College, Fujian province university, Xiamen 361023, China.
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Jung UJ. Sarcopenic Obesity: Involvement of Oxidative Stress and Beneficial Role of Antioxidant Flavonoids. Antioxidants (Basel) 2023; 12:antiox12051063. [PMID: 37237929 DOI: 10.3390/antiox12051063] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/25/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
Sarcopenic obesity, which refers to concurrent sarcopenia and obesity, is characterized by decreased muscle mass, strength, and performance along with abnormally excessive fat mass. Sarcopenic obesity has received considerable attention as a major health threat in older people. However, it has recently become a health problem in the general population. Sarcopenic obesity is a major risk factor for metabolic syndrome and other complications such as osteoarthritis, osteoporosis, liver disease, lung disease, renal disease, mental disease and functional disability. The pathogenesis of sarcopenic obesity is multifactorial and complicated, and it is caused by insulin resistance, inflammation, hormonal changes, decreased physical activity, poor diet and aging. Oxidative stress is a core mechanism underlying sarcopenic obesity. Some evidence indicates a protective role of antioxidant flavonoids in sarcopenic obesity, although the precise mechanisms remain unclear. This review summarizes the general characteristics and pathophysiology of sarcopenic obesity and focuses on the role of oxidative stress in sarcopenic obesity. The potential benefits of flavonoids in sarcopenic obesity have also been discussed.
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Affiliation(s)
- Un Ju Jung
- Department of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, Republic of Korea
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Punmiya A, Prabhu A. Structural fingerprinting of pleiotropic flavonoids for multifaceted Alzheimer's disease. Neurochem Int 2023; 163:105486. [PMID: 36641110 DOI: 10.1016/j.neuint.2023.105486] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 12/13/2022] [Accepted: 01/09/2023] [Indexed: 01/13/2023]
Abstract
Alzheimer's disease has emerged as one of the most challenging neurodegenerative diseases associated with dementia, loss of cognitive functioning and memory impairment. Despite enormous efforts to identify disease modifying technologies, the repertoire of currently approved drugs consists of a few symptomatic candidates that are not capable of halting disease progression. Moreover, these single mechanism drugs target only a small part of the pathological cascade and do not address most of the etiological basis of the disease. Development of therapies that are able to simultaneously tackle all the multiple interlinked causative factors such as amyloid protein aggregation, tau hyperphosphorylation, cholinergic deficit, oxidative stress, metal dyshomeostasis and neuro-inflammation has become the focus of intensive research in this domain. Flavonoids are natural phytochemicals that have demonstrated immense potential as medicinal agents due to their multiple beneficial therapeutic effects. The polypharmacological profile of flavonoids aligns well with the multifactorial pathological landscape of Alzheimer's disease, making them promising candidates to overcome the challenges of this neurodegenerative disorder. This review presents a detailed overview of the pleiotropic biology of flavonoids favourable for Alzheimer therapeutics and the structural basis for these effects. Structure activity trends for several flavonoid classes such as flavones, flavonols, flavanones, isoflavones, flavanols and anthocyanins are comprehensively analyzed in detail and presented.
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Affiliation(s)
- Amisha Punmiya
- Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
| | - Arati Prabhu
- Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India.
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In vitro cytotoxic and antioxidant evaluation of quercetin loaded in ionic cross-linked chitosan nanoparticles. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103561] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Lin HJ, Mahendran R, Huang HY, Chiu PL, Chang YM, Day CH, Chen RJ, Padma VV, Liang-Yo Y, Kuo WW, Huang CY. Aqueous extract of Solanum nigrum attenuates Angiotensin-II induced cardiac hypertrophy and improves cardiac function by repressing protein kinase C-ζ to restore HSF2 deSUMOlyation and Mel-18-IGF-IIR signaling suppression. JOURNAL OF ETHNOPHARMACOLOGY 2022; 284:114728. [PMID: 34634367 DOI: 10.1016/j.jep.2021.114728] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Solanum nigrum, commonly known as Makoi or black shade has been traditionally used in Asian countries and other regions of world to treat liver disorders, diarrhoea, inflammatory conditions, chronic skin ailments (psoriasis and ringworm), fever, hydrophobia, painful periods, eye diseases, etc. It has been observed that S. nigrum contains substances, like steroidal saponins, total alkaloid, steroid alkaloid, and glycoprotein, which show anti-tumor activity. However; there is no scientific evidence of the efficacy of S. nigrum in the treatment of cardiac hypertrophy. AIM To investigate the ability of S. nigrum to attenuate Angiotensin II - induced cardiac hypertrophy and improve cardiac function through the suppression of protein kinase PKC-ζ and Mel-18-IGF-IIR signaling leading to the restoration of HSF2 desumolyation. MATERIALS AND METHODS Cardiomyoblast cells (H9c2) were challenged with 100 nM Angiotensin-II (AngII) for 24 h and were then treated with different concentration of S.nigrum or Calphostin C for 24 h. The hypertrophic effect in cardiomyoblast cells were determined by immunofluorescence staining and the modulations in hypertrophic protein marker along with Protein Kinase C-ζ, MEL18, HSF2, and Insulin like growth factor II (IGFIIR), markers were analyzed by western blotting. In vivo experiments were performed using 12 week old male Wistar Kyoto rats (WKY) and Spontaneously hypertensive rats (SHR) separated into five groups. [1]Control WKY, [2] WKY -100 mg/kg of S.nigrum treatment, [3] SHR, [4] SHR-100 mg/kg of S.nigrum treatment, [5] SHR-300 mg/kg of S.nigrum treatment. S. nigrum was administered intraperitoneally for 8 week time interval. RESULTS Western blotting results indicate that S. nigrum significantly attenuates AngII induced cardiac hypertrophy. Furthermore, actin staining confirmed the ability of S. nigrum to ameliorate AngII induced cardiac hypertrophy. Moreover, S. nigrum administration suppressed the hypertrophic signaling mediators like Protein Kinase C-ζ, Mel-18, and IGFIIR in a dose-dependent manner and HSF2 activation (restore deSUMOlyation) that leads to downregulation of IGF-IIR expression. Additionally in vivo experiments demonstrate the reduced heart sizes of S. nigrum treated SHRs rats when compared to control WKY rats. CONCLUSION Collectively, the data reveals the cardioprotective effect of S. nigrum inhibiting PKC-ζ with alleviated IGF IIR level in the heart that profoundly remits cardiac hypertrophy for hypertension-induced heart failure.
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Affiliation(s)
- Hung-Jen Lin
- School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ramasamy Mahendran
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Hsiang-Yen Huang
- Graduate Institute of Basic Medical Science, China Medical University, Taichung City, 40402, Taiwan, ROC
| | - Ping-Ling Chiu
- Ept Douliu Chinese Medical Clinic, Douliu, Taiwan; 1PT Biotechnology Co., Ltd., Taichung, Taiwan
| | - Yung-Ming Chang
- 1PT Biotechnology Co., Ltd., Taichung, Taiwan; The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan
| | - Cecilia Hsuan Day
- Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan
| | - Ray-Jade Chen
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - V Vijaya Padma
- Department of Biotechnology, Bharathiar University, Coimbatore, India
| | - Yang Liang-Yo
- Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Laboratory for Neural Repair, China Medical University Hospital, Taichung, Taiwan
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichuang, 406, Taiwan; Ph.D. Program for Biotechnology Industry, China Medical University, Taichuang, 406, Taiwan
| | - Chih-Yang Huang
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichuang, 406, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, 970, Taiwan.
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Slika H, Mansour H, Wehbe N, Nasser SA, Iratni R, Nasrallah G, Shaito A, Ghaddar T, Kobeissy F, Eid AH. Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomed Pharmacother 2022; 146:112442. [PMID: 35062053 DOI: 10.1016/j.biopha.2021.112442] [Citation(s) in RCA: 206] [Impact Index Per Article: 68.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 12/14/2022] Open
Abstract
Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy.
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Affiliation(s)
- Hasan Slika
- Department of Pharmacology and Toxicology, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon.
| | - Hadi Mansour
- Department of Pharmacology and Toxicology, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon.
| | - Nadine Wehbe
- Department of Biology, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon.
| | - Suzanne A Nasser
- Department of Pharmacology and Therapeutics, Beirut Arab University, P.O. Box 11-5020, Beirut, Lebanon.
| | - Rabah Iratni
- Department of Biology, College of Science, United Arab Emirates University, P.O. Box 15551, Al-Ain, United Arab Emirates.
| | - Gheyath Nasrallah
- Department of Biomedical Sciences, College of Health Sciences, Qatar University, P.O. Box: 2713, Doha, Qatar.
| | - Abdullah Shaito
- Biomedical Research Center, Qatar University, P.O. Box: 2713, Doha, Qatar.
| | - Tarek Ghaddar
- Department of Chemistry, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon.
| | - Firas Kobeissy
- Department of Biochemistry and Molecular Genetics, American University of Beirut, P.O. Box: 11-0236, Beirut, Lebanon.
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
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Rodriguez S, Skeet K, Mehmetoglu-Gurbuz T, Goldfarb M, Karri S, Rocha J, Shahinian M, Yazadi A, Poudel S, Subramani R. Phytochemicals as an Alternative or Integrative Option, in Conjunction with Conventional Treatments for Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13225753. [PMID: 34830907 PMCID: PMC8616323 DOI: 10.3390/cancers13225753] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/10/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is globally ranked as the sixth most diagnosed cancer, and the second most deadly cancer. To worsen matters, there are only limited therapeutic options currently available; therefore, it is necessary to find a reservoir from which new HCC treatments may be acquired. The field of phytomedicine may be the solution to this problem, as it offers an abundance of plant-derived molecules, which show capabilities of being effective against HCC proliferation, invasion, migration, and metastasis. In our review, we collect and analyze current evidence regarding these promising phytochemical effects on HCC, and delve into their potential as future chemotherapies. Additionally, information on the signaling behind these numerous phytochemicals is provided, in an attempt to understand their mechanisms. This review makes accessible the current body of knowledge pertaining to phytochemicals as HCC treatments, in order to serve as a reference and inspiration for further research into this subject. Abstract Hepatocellular carcinoma (HCC) is the most abundant form of liver cancer. It accounts for 75–85% of liver cancer cases and, though it ranks globally as the sixth most common cancer, it ranks second in cancer-related mortality. Deaths from HCC are usually due to metastatic spread of the cancer. Unfortunately, there are many challenges and limitations with the latest HCC therapies and medications, making it difficult for patients to receive life-prolonging care. As there is clearly a high demand for alternative therapy options for HCC, it is prudent to turn to plants for the solution, as their phytochemicals have long been used and revered for their many medicinal purposes. This review explores the promising phytochemical compounds identified from pre-clinical and clinical trials being used either independently or in conjunction with already existing cancer therapy treatments. The phytochemicals discussed in this review were classified into several categories: lipids, polyphenols, alkaloids, polysaccharides, whole extracts, and phytochemical combinations. Almost 80% of the compounds failed to progress into clinical studies due to lack of information regarding the toxicity to normal cells and bioavailability. Although large obstacles remain, phytochemicals can be used either as an alternative or integrative therapy in conjunction with existing HCC chemotherapies. In conclusion, phytochemicals have great potential as treatment options for hepatocellular carcinoma.
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Affiliation(s)
- Sheryl Rodriguez
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Kristy Skeet
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Tugba Mehmetoglu-Gurbuz
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Madeline Goldfarb
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (M.G.); (S.K.)
| | - Shri Karri
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (M.G.); (S.K.)
| | - Jackelyn Rocha
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Mark Shahinian
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Abdallah Yazadi
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Seeta Poudel
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Ramadevi Subramani
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
- Correspondence: ; Tel.: +1-915-215-6851
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11
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Zeng J, Li M, Xu JY, Xiao H, Yang X, Fan JX, Wu K, Chen S. Aberrant ROS Mediate Cell Cycle and Motility in Colorectal Cancer Cells Through an Oncogenic CXCL14 Signaling Pathway. Front Pharmacol 2021; 12:764015. [PMID: 34744744 PMCID: PMC8563703 DOI: 10.3389/fphar.2021.764015] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/04/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Reactive oxygen species (ROS) act as signal mediators to induce tumorigenesis. Objective: This study aims to explore whether chemokine CXCL14 is involved in the proliferation and migration of ROS-induced colorectal cancer (CRC) cells. Methods: The proliferative and migratory capacities of CRC cells treated with or without H2O2 were measured by various methods, including the CKK-8 assay, colony formation assay, flow cytometry, wounding healing assay, and migration assay. Results: The results revealed that H2O2 promoted the proliferation and migration of CRC cells by regulating the cell cycle progression and the epithelial to mesenchymal transition (EMT) process. Furthermore, we noted that the expression level of CXCL14 was elevated in both HCT116 cells and SW620 cells treated with H2O2. An antioxidant N-Acetyl-l-cysteine (NAC) pretreatment could partially suppress the CXCL14 expression in CRC cells treated with H2O2. Next, we constructed CRC cell lines stably expressing CXCL14 (HCT116/CXCL14 and SW620/CXCL14) and CRC cell lines with empty plasmid vectors (HCT116/Control and SW620/Control) separately. We noted that both H2O2 treatment and CXCL14 over-expression could up-regulate the expression levels of cell cycle-related and EMT-related proteins. Moreover, the level of phosphorylated ERK (p-ERK) was markedly higher in HCT116/CXCL14 cells when compared with that in HCT116/Control cells. CXCL14-deficiency significantly inhibited the phosphorylation of ERK compared with control (i.e., scrambled shNCs). H2O2 treatment could partially restore the expression levels of CXCL14 and p-ERK in HCT116/shCXCL14 cells. Conclusion: Our studies thus suggest that aberrant ROS may promote colorectal cancer cell proliferation and migration through an oncogenic CXCL14 signaling pathway.
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Affiliation(s)
- Jun Zeng
- Department of Genetics and Cell Biology, College of Life Sciences, Chongqing Normal University, Chongqing, China
| | - Mei Li
- Department of Genetics and Cell Biology, College of Life Sciences, Chongqing Normal University, Chongqing, China
| | - Jun-Yu Xu
- Department of Genetics and Cell Biology, College of Life Sciences, Chongqing Normal University, Chongqing, China
| | - Heng Xiao
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xian Yang
- Department of Genetics and Cell Biology, College of Life Sciences, Chongqing Normal University, Chongqing, China
| | - Jiao-Xiu Fan
- Department of Genetics and Cell Biology, College of Life Sciences, Chongqing Normal University, Chongqing, China
| | - Kang Wu
- Shenzhen Luohu People's Hospital, the Third Affiliated Hospital of Shenzhen University, Shenzhen, China.,South China Hospital, Shenzhen University, Shenzhen, China
| | - Shuang Chen
- Department of Dermatovenereology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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12
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Sorolla MA, Hidalgo I, Sorolla A, Montal R, Pallisé O, Salud A, Parisi E. Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities. Cancers (Basel) 2021; 13:5037. [PMID: 34680186 PMCID: PMC8534037 DOI: 10.3390/cancers13205037] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the fourth most common cause of cancer deaths worldwide. Although screening programs have reduced mortality rates, there is a need for research focused on finding the main factors that lead primary CRC to progress and metastasize. During tumor progression, malignant cells modify their habitat, corrupting or transforming cells of different origins and creating the tumor microenvironment (TME). Cells forming the TME like macrophages, neutrophils, and fibroblasts generate reactive oxygen species (ROS) that modify the cancer niche. The effects of ROS in cancer are very diverse: they promote cellular proliferation, epithelial-to-mesenchymal transition (EMT), evasion of cell death programs, migration, and angiogenesis. Due to the multifaceted role of ROS in cancer cell survival and function, ROS-modulating agents such as antioxidants or pro-oxidants could have therapeutic potential in cancer prevention and/or as a complement to systemic treatments. In this review, we will examine the main ROS producer cells and their effects on cancer progression and metastasis. Furthermore, we will enumerate the latest clinical trials where pro-oxidants and antioxidants have therapeutic uses in CRC.
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Affiliation(s)
- Maria Alba Sorolla
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
| | - Ivan Hidalgo
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
| | - Anabel Sorolla
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
| | - Robert Montal
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
- Department of Medical Oncology, Arnau de Vilanova University Hospital (HUAV), 25198 Lleida, Spain
| | - Ona Pallisé
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
- Department of Medical Oncology, Arnau de Vilanova University Hospital (HUAV), 25198 Lleida, Spain
| | - Antonieta Salud
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
- Department of Medical Oncology, Arnau de Vilanova University Hospital (HUAV), 25198 Lleida, Spain
| | - Eva Parisi
- Research Group of Cancer Biomarkers, Biomedical Research Institute of Lleida (IRBLleida), 25198 Lleida, Spain; (M.A.S.); (I.H.); (A.S.); (R.M.); (O.P.); (A.S.)
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13
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Soofiyani SR, Hosseini K, Forouhandeh H, Ghasemnejad T, Tarhriz V, Asgharian P, Reiner Ž, Sharifi-Rad J, Cho WC. Quercetin as a Novel Therapeutic Approach for Lymphoma. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:3157867. [PMID: 34381559 PMCID: PMC8352693 DOI: 10.1155/2021/3157867] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 06/15/2021] [Accepted: 07/12/2021] [Indexed: 11/19/2022]
Abstract
Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin's lymphoma and non-Hodgkin's lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.
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Affiliation(s)
- Saiedeh Razi Soofiyani
- Clinical Research Development Unit of Sina Educational, Research, and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kamran Hosseini
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Haleh Forouhandeh
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Tohid Ghasemnejad
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahideh Tarhriz
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parina Asgharian
- Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Željko Reiner
- Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
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14
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Singh RK, Verma PK, Kumar A, Kumar S, Acharya A. Achyranthes aspera L. leaf extract induced anticancer effects on Dalton's Lymphoma via regulation of PKCα signaling pathway and mitochondrial apoptosis. JOURNAL OF ETHNOPHARMACOLOGY 2021; 274:114060. [PMID: 33771640 DOI: 10.1016/j.jep.2021.114060] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/06/2021] [Accepted: 03/18/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Epidemiological studies promote the inclusion of natural-products in diet due to their inhibitory effects on various types of cancer. Among them, Achyranthes aspera L. (Family Amaranthaceae) is a medicinal plant in Ayurvedic pharmacopeia, found in India, Southeast Asia, America, and Sub-Saharan Africa. It is endowed with anti-inflammatory, anti-oxidant, and anti-cancer activities. However, its potential effect on Non-Hodgkin lymphomas (NHLs), has not yet been clarified. AIM OF THE STUDY In the present study, we aimed to investigate the effect of Achyranthes aspera L. leaf extracts on highly aggressive murine NHL called Dalton's Lymphoma (DL) in vitro and in vivo. MATERIAL AND METHODS GC-HRMS analysis was carried out for the identification of compounds present in A. aspera leaf extract. The cytotoxicity of various A. aspera leaf extracts was evaluated on DL cells by MTT assay. Chromatin condensation, nuclear fragmentation, and morphological changes were observed by microscopy technique. Flow cytometry was used to measure the changes in mitochondrial membrane potential (ΔΨm) and apoptosis. In addition, the expressions of apoptosis-related proteins were detected by western blotting. Meanwhile, the in vivo anti-tumor effect of leaf extract was tested in DL induced Balb/c mice. RESULT GC-HRMS analysis of A. aspera methanolic leaf extract (AAML) revealed the presence of ten pharmacologically active compounds. The results showed that AAML suppressed cell proliferation, decreased mitochondrial membrane potential, changed the morphological structure, and induced apoptosis. Moreover, AAML could promote the release of cytochrome c by regulating Bcl-2 family proteins and then activated caspase-9/ -3 to triggered cell apoptosis. At the same time in DL cells treated with AAML, the protein kinase Cα (PKCα) pathway was inhibited in a concentration-dependent manner. Remarkably, in vivo, AAML mediated suppression of DL growth in Balb/c mice was accompanied by attenuation of the PKCα pathway and induction of apoptosis. Our result suggested that AAML promotes mitochondrial apoptotic cascade in DL cells by suppressing the PKCα signaling pathway. CONCLUSION The study suggests that AAML could potently suppress DL progression by promoting apoptosis via mitochondrial-cascade and attenuation of the PKCα signaling pathway.
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Affiliation(s)
- Rishi Kant Singh
- Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India
| | - Praveen Kumar Verma
- Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India
| | - Amit Kumar
- Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India
| | - Sandeep Kumar
- Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India
| | - Arbind Acharya
- Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, U.P, India.
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15
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Huang M, Wang Y, Ahmad M, Ying R, Wang Y, Tan C. Fabrication of pickering high internal phase emulsions stabilized by pecan protein/xanthan gum for enhanced stability and bioaccessibility of quercetin. Food Chem 2021; 357:129732. [PMID: 33872869 DOI: 10.1016/j.foodchem.2021.129732] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 03/08/2021] [Accepted: 03/26/2021] [Indexed: 11/25/2022]
Abstract
The stabilizing effect of pecan protein (PP)/xanthan gum (XG) complex on the Pickering high internal phase emulsion (HIPE) has been examined in this study. Shear viscosity of HIPEs increased with respect to XG concentration due to the formation of hydrogen bonds between PP and XG. Confocal laser scanning microscopy (CLSM) imaging showed fairly even distribution and polygonal shapes of oil droplets (30-70 μm). When used to encapsulate quercetin, this Pickering HIPE exhibited high retention rate and improved gel strength. Furthermore, the interface film of PP/XG on oil-water interface contributed to the high retention of quercetin in Pickering HIPEs when exposure to heat, iron ions, and hydrogen peroxide in aqueous phase. The bioaccessibility of quercetin after in vitro simulated digestion were also improved by HIPE encapsulation than that in oil. To conclude, PP/XG complex stabilized HIPEs may be suitable delivery systems for improving colloidal stability and bioaccessibility of hydrophobic bioactives.
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Affiliation(s)
- Meigui Huang
- Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China
| | - Yu Wang
- Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China
| | - Mehraj Ahmad
- Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China
| | - Ruifeng Ying
- Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China
| | - Yaosong Wang
- Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China
| | - Chen Tan
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University (BTBU), Beijing 100048, China.
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16
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Dükel M, Tavsan Z, Kayali HA. Flavonoids regulate cell death-related cellular signaling via ROS in human colon cancer cells. Process Biochem 2021. [DOI: 10.1016/j.procbio.2020.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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17
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Zhang YM, Zhang ZY, Wang RX. Protective Mechanisms of Quercetin Against Myocardial Ischemia Reperfusion Injury. Front Physiol 2020; 11:956. [PMID: 32848878 PMCID: PMC7412593 DOI: 10.3389/fphys.2020.00956] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 07/15/2020] [Indexed: 12/13/2022] Open
Abstract
Quercetin has attracted more attention in recent years due to its protective role against ischemia/reperfusion injury. Quercetin can alleviate oxidative stress injury through the inhibition of NADPH oxidase and xanthine oxidase, blockage of the Fenton reaction, and scavenging of reactive oxygen species. Quercetin can also exert anti-inflammatory and anti-apoptotic effects by reducing the response to inflammatory factors and inhibiting cell apoptosis. Moreover, it can induce vasodilation effects through the inhibition of endothelin-1 receptors, the enhancement of NO stimulation and the activation of the large-conductance calcium-activated potassium channels. Finally, Quercetin can also antagonize the calcium overload. These multifaceted activities of Quercetin make it a potential therapeutic alternative for the treatment of ischemia/reperfusion injury.
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Affiliation(s)
- Yu-Min Zhang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Zhen-Ye Zhang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Ru-Xing Wang
- Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China
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18
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Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, Merghany RM, El Mahdy NM, Kılıç CS, Sytar O, Sharifi-Rad M, Sharopov F, Martins N, Martorell M, Cho WC. Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health. ACS OMEGA 2020; 5:11849-11872. [PMID: 32478277 PMCID: PMC7254783 DOI: 10.1021/acsomega.0c01818] [Citation(s) in RCA: 312] [Impact Index Per Article: 62.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 05/01/2020] [Indexed: 05/03/2023]
Abstract
Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.
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Affiliation(s)
- Bahare Salehi
- Student
Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran
| | - Laura Machin
- Institute
of Pharmacy and Food, University of Havana, Havana, Cuba
| | - Lianet Monzote
- Parasitology
Department, Institute of Medicine Tropical
Pedro Kourí, Havana, Cuba
| | - Javad Sharifi-Rad
- Phytochemistry
Research Center, Shahid Beheshti University
of Medical Sciences, Tehran 1991953381, Iran
| | - Shahira M. Ezzat
- Department
of Pharmacognosy, Faculty of Pharmacy, Cairo
University, Kasr El-Aini
Street, Cairo 11562, Egypt
- Department
of Pharmacognosy, Faculty of Pharmacy, October
University for Modern Sciences and Arts (MSA), 6th October 12566, Egypt
| | - Mohamed A. Salem
- Department
of Pharmacognosy, Faculty of Pharmacy, Menoufia
University, Gamal Abd
El Nasr st., Shibin Elkom, Menoufia 32511, Egypt
| | - Rana M. Merghany
- Department
of Pharmacognosy, National Research Centre, Giza 12622, Egypt
| | - Nihal M. El Mahdy
- Department
of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 6th of October 12566, Egypt
| | - Ceyda Sibel Kılıç
- Department
of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey
| | - Oksana Sytar
- Department of Plant Biology Department, Institute of Biology, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, Kyiv 01033, Ukraine
- Department of Plant Physiology, Slovak
University of Agriculture, Nitra, A. Hlinku 2, Nitra 94976, Slovak Republic
| | - Mehdi Sharifi-Rad
- Department
of Medical Parasitology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman 7616913555, Iran
| | - Farukh Sharopov
- Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki 139, Dushanbe 734003, Tajikistan
| | - Natália Martins
- Faculty of Medicine, University
of Porto, Porto 4200-319, Portugal
- Institute
for Research and Innovation in Health (i3S), University of Porto, Porto 4200-135, Portugal
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy,
and Centre
for Healthy Living, University of Concepción, Concepción 4070386, Chile
- Universidad de Concepción, Unidad
de Desarrollo Tecnológico,
UDT, Concepción 4070386, Chile
| | - William C. Cho
- Department
of Clinical Oncology, Queen
Elizabeth Hospital, 30
Gascoigne Road, Kowloon, Hong
Kong
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19
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Aussem A, Ludwig K. The Potential for Reducing Lynch Syndrome Cancer Risk with Nutritional Nrf2 Activators. Nutr Cancer 2020; 73:404-419. [PMID: 32281399 DOI: 10.1080/01635581.2020.1751215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Lynch syndrome (LS), is an autosomal dominant disorder predisposing patients to multiple cancers, predominantly colorectal (CRC) and endometrial, and is implicated in 2-4% of all CRC cases. LS is characterized by mutations of four mismatch repair (MMR) genes which code for proteins responsible for recognizing and repairing DNA lesions occurring through multiple mechanisms including oxidative stress (OS). Increased OS can cause DNA mutations and is considered carcinogenic. Due to reduced MMR activity, LS patients have an increased risk of cancer as a result of a decreased ability to recognize and repair DNA lesions caused by OS. Due to its carcinogenic properties, reducing the level of OS may reduce the risk of cancer. Nutritional Nrf2 activators have been shown to reduce the risk of carcinogenesis in the general population through activation of the endogenous antioxidant system. Common nutritional Nrf2 activators include sulforaphane, curcumin, DATS, quercetin, resveratrol, and EGCG. Since LS patients are more susceptible to carcinogenesis caused by OS, it is hypothesized that nutritional Nrf2 activators may have the potential to reduce the risk of cancer in those with LS by modulating OS and inflammation. The purpose of this paper is to review the available evidence in support of this statement.
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Affiliation(s)
- Andrew Aussem
- Hawthorn University, Whitethorn, California, USA.,McMaster University, Hamilton, Canada
| | - Kirsten Ludwig
- Hawthorn University, Whitethorn, California, USA.,Semel Institute for Neuroscience and Behaviour, University of California, Los Angeles, California, USA
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20
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Vinayak M, Maurya AK. Quercetin Loaded Nanoparticles in Targeting Cancer: Recent Development. Anticancer Agents Med Chem 2020; 19:1560-1576. [PMID: 31284873 DOI: 10.2174/1871520619666190705150214] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 05/23/2019] [Accepted: 05/23/2019] [Indexed: 12/27/2022]
Abstract
The spread of metastatic cancer cell is the main cause of death worldwide. Cellular and molecular basis of the action of phytochemicals in the modulation of metastatic cancer highlights the importance of fruits and vegetables. Quercetin is a natural bioflavonoid present in fruits, vegetables, seeds, berries, and tea. The cancer-preventive activity of quercetin is well documented due to its anti-inflammatory, anti-proliferative and anti-angiogenic activities. However, poor water solubility and delivery, chemical instability, short half-life, and low-bioavailability of quercetin limit its clinical application in cancer chemoprevention. A better understanding of the molecular mechanism of controlled and regulated drug delivery is essential for the development of novel and effective therapies. To overcome the limitations of accessibility by quercetin, it can be delivered as nanoconjugated quercetin. Nanoconjugated quercetin has attracted much attention due to its controlled drug release, long retention in tumor, enhanced anticancer potential, and promising clinical application. The pharmacological effect of quercetin conjugated nanoparticles typically depends on drug carriers used such as liposomes, silver nanoparticles, silica nanoparticles, PLGA (Poly lactic-co-glycolic acid), PLA (poly(D,L-lactic acid)) nanoparticles, polymeric micelles, chitosan nanoparticles, etc. In this review, we described various delivery systems of nanoconjugated quercetin like liposomes, silver nanoparticles, PLGA (Poly lactic-co-glycolic acid), and polymeric micelles including DOX conjugated micelles, metal conjugated micelles, nucleic acid conjugated micelles, and antibody-conjugated micelles on in vitro and in vivo tumor models; as well as validated their potential as promising onco-therapeutic agents in light of recent updates.
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Affiliation(s)
- Manjula Vinayak
- Biochemistry & Molecular Biology Laboratory, Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, India
| | - Akhilendra K Maurya
- Biochemistry & Molecular Biology Laboratory, Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, India.,Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States
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21
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Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease. Life Sci 2019; 224:109-119. [PMID: 30914316 DOI: 10.1016/j.lfs.2019.03.055] [Citation(s) in RCA: 190] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/22/2019] [Accepted: 03/22/2019] [Indexed: 12/17/2022]
Abstract
Quercetin belongs to the flavonoids family, which is present in most of the plants including fruits, vegetables, green tea and even in red wine having antioxidant activities. It is available as a food supplement in the market and has physiological health effects. Quercetin has anti-inflammatory, anticancer and anti-prostate activities along with its beneficial effects on high cholesterol, kidney transplantation, asthma, diabetes, viral infections, pulmonary, schizophrenia and cardiovascular diseases. Quercetin possesses scavenging potential of hydroxyl radical (OH-), hydrogen peroxide (H2O2), and superoxide anion (O2-). These reactive oxygen species (ROS) hampers lipid, protein, amino acids and deoxyribonucleic acid (DNA) processing leading to epigenetic alterations. Quercetin has the ability to combat these harmful effects. ROS plays a vital role in the progression of Alzheimer's disease (AD), and we propose that quercetin would be the best choice to overcome cellular and molecular signals in regulating normal physiological functions. However, data are not well documented regarding exact cellular mechanisms of quercetin. The neuroprotective effects of quercetin are mainly due to potential up- and/or down-regulation of cytokines via nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Paraoxonase-2, c-Jun N-terminal kinase (JNK), Protein kinase C, Mitogen-activated protein kinase (MAPK) signalling cascades, and PI3K/Akt pathways. Therefore, the aim of the present review was to elaborate on the cellular and molecular mechanisms of the quercetin involved in the protection against AD.
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Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application. Molecules 2019; 24:E1123. [PMID: 30901869 PMCID: PMC6470739 DOI: 10.3390/molecules24061123] [Citation(s) in RCA: 678] [Impact Index Per Article: 113.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 03/18/2019] [Accepted: 03/19/2019] [Indexed: 01/14/2023] Open
Abstract
Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
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Affiliation(s)
- Dong Xu
- Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
| | - Meng-Jiao Hu
- Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
| | - Yan-Qiu Wang
- Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
| | - Yuan-Lu Cui
- Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
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Yuan SF, Alper HS. Metabolic engineering of microbial cell factories for production of nutraceuticals. Microb Cell Fact 2019; 18:46. [PMID: 30857533 PMCID: PMC6410520 DOI: 10.1186/s12934-019-1096-y] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 02/27/2019] [Indexed: 11/18/2022] Open
Abstract
Metabolic engineering allows for the rewiring of basic metabolism to overproduce both native and non-native metabolites. Among these biomolecules, nutraceuticals have received considerable interest due to their health-promoting or disease-preventing properties. Likewise, microbial engineering efforts to produce these value-added nutraceuticals overcome traditional limitations of low yield from extractions and complex chemical syntheses. This review covers current strategies of metabolic engineering employed for the production of a few key nutraceuticals with selecting polyunsaturated fatty acids, polyphenolic compounds, carotenoids and non-proteinogenic amino acids as exemplary molecules. We focus on the use of both mono-culture and co-culture strategies to produce these molecules of interest. In each of these cases, metabolic engineering efforts are enabling rapid production of these molecules.
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Affiliation(s)
- Shuo-Fu Yuan
- Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA
| | - Hal S Alper
- Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
- McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, TX, 78712, USA.
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Umrao S, Maurya A, Shukla V, Grigoriev A, Ahuja R, Vinayak M, Srivastava R, Saxena P, Oh IK, Srivastava A. Anticarcinogenic activity of blue fluorescent hexagonal boron nitride quantum dots: as an effective enhancer for DNA cleavage activity of anticancer drug doxorubicin. Mater Today Bio 2019; 1:100001. [PMID: 32159136 PMCID: PMC7061680 DOI: 10.1016/j.mtbio.2019.01.001] [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: 11/10/2018] [Revised: 12/19/2018] [Accepted: 01/28/2019] [Indexed: 12/13/2022] Open
Abstract
Blue fluorescent hexagonal boron nitride quantum dots (h-BNQDs) of ∼10 nm size as an effective enhancer for DNA cleavage activity of anticancer drug doxorubicin (DOX) were synthesized using simple one-step hydrothermal disintegration of exfoliated hexagonal boron nitride at very low temperature ∼ 120 °C. Boron nitride quantum dots (BNQDs) at a concentration of 25 μg/ml enhanced DNA cleavage activity of DOX up to 70% as checked by converting supercoiled fragment into nicked circular PBR322 DNA. The interaction of BNQDs with DOX is proportional to the concentration of BNQDs, with binding constant K b ∼0.07338 μg/ml. In addition, ab initio theoretical results indicate that DOX is absorbed on BNQDs at the N-terminated edge with binding energy -1.075 eV and prevented the normal replication mechanisms in DNA. BNQDs have been shown to kill the breast cancer cell MCF-7 extensively as compared with the normal human keratinocyte cell HaCaT. The cytotoxicity of BNQDs may be correlated with reduced reactive oxygen species level and increased apoptosis in MCF-7 cells, which may be liable to enhance the anticancerous activity of DOX. The results provide a base to develop BNQD-DOX as a more effective anticancer drug.
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Affiliation(s)
- S. Umrao
- Department of Physics, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
- Creative Research Initiative Center for Functionally Antagonistic Nano-Engineering, Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - A.K. Maurya
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - V. Shukla
- Condensed Matter Theory Group, Department of Physics and Astronomy, Uppsala University, Box 516, 75120, Uppsala, Sweden
| | - A. Grigoriev
- Condensed Matter Theory Group, Department of Physics and Astronomy, Uppsala University, Box 516, 75120, Uppsala, Sweden
| | - R. Ahuja
- Condensed Matter Theory Group, Department of Physics and Astronomy, Uppsala University, Box 516, 75120, Uppsala, Sweden
| | - M. Vinayak
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - R.R. Srivastava
- Department of Physics, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - P.S. Saxena
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - I.-K. Oh
- Creative Research Initiative Center for Functionally Antagonistic Nano-Engineering, Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - A. Srivastava
- Department of Physics, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
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Vinayak M. Molecular Action of Herbal Antioxidants in Regulation of Cancer Growth: Scope for Novel Anticancer Drugs. Nutr Cancer 2018; 70:1199-1209. [DOI: 10.1080/01635581.2018.1539187] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Manjula Vinayak
- Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
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Improved synergistic anticancer efficacy of quercetin in combination with PI-103, rottlerin, and G0 6983 against MCF-7 and RAW 264.7 cells. In Vitro Cell Dev Biol Anim 2018; 55:36-44. [PMID: 30413935 DOI: 10.1007/s11626-018-0309-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 11/01/2018] [Indexed: 01/21/2023]
Abstract
Flavonoids have been chronicles of the history of a long way journey in the cure of physiological or pathophysiological conditions in various diseases including cancer. Our previous findings suggest the extensive mechanism of quercetin (QUE) mediated regression of cell survival, cell proliferation, oxidative stress, inflammation, and angiogenesis via modulating PI3K and PKC signaling in lymphoma as well as hepatocellular carcinoma. PI3K-PKC pathway is a key monitor of mammalian cells regulated by its different isoenzymes, which may exert similar or opposite cellular effects by differential coupling of signaling pathways. Put forward the invention of selective inhibitors against various isoenzymes is beneficial to reduce the burden of inclusive deleterious effects of drug for normal physiological process. Therefore, we hypothesized the improved anticancer efficacy of QUE in combination with isoenzyme inhibitors-rottlerin (ROT-PKCδ inhibitor), G0 6983 (PKCα inhibitor), and PI-103 (p110α-class I PI3K inhibitor) in MCF-7 and RAW 264.7 cells. QUE significantly improves the cytotoxicity of ROT + G0 6983 ranged 30-55% and PI-103 ranged 24-63% after 24-48 h against MCF-7 cells. Additionally in the presence of QUE, the improved cytotoxicity of ROT + G0 6983 is observed to range 69-75% and PI-103 ranged 45-88% after 24-48 h in RAW 264.7 cells. This increment in cell deaths are positively correlated with enhanced morphological alteration observed in MCF-7 cells. Further, QUE significantly increases the attenuation of PKCα level approximately by 50% in combination with PI-103. Overall results of the current study suggested that QUE improves the synergistic anticancer efficacy in combination with PI-103, ROT, and G0 6983 in MCF-7 and RAW 264.7 cells.
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The In Vitro Anti-Proliferative Interaction of Flavonoid Quercetin and Toxic Metal Cadmium in the 1321N1 Human Astrocytoma Cell Line. Sci Pharm 2018; 86:scipharm86030036. [PMID: 30201909 DOI: 10.3390/scipharm86030036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 09/04/2018] [Accepted: 09/05/2018] [Indexed: 01/08/2023] Open
Abstract
Cadmium (Cd) is a toxic heavy metal occurring in the environment as an industrial pollutant. The systematic accumulation of Cd in the human body may lead to major health problems. Quercetin (QE) is a natural flavonoid widely distributed in plants and is a part of human diet. Many studies have demonstrated the multiple benefits of QE to humans in protecting cells of our bodies. The aim of this study was to investigate the effect of QE and Cd on the proliferation of astrocytoma 1321N1 cells. Results indicated that the simultaneous exposure of the cells to 200 µM QE and 16 μM Cd significantly reduced cell viability to 6.9 ± 1.6% with respect to vehicle-treated cells. Other experiments of QE pre-treatment followed by the exposure to Cd alone or with QE indicated significant but decreased ability of QE or Cd to reduce proliferation of the cells compared to their co-incubation. Our study suggested a synergetic anti-proliferative interaction of Cd and QE in malignantly transformed cells. This adds new information regarding the biological effects of QE.
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He D, Zhang P, Sai X, Li X, Wang L, Xu Y. Camellia euphlebia flower extract inhibits oleic acid-induced lipid accumulation via reduction of lipogenesis in HepG2 cells. Eur J Integr Med 2018. [DOI: 10.1016/j.eujim.2017.11.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Modulation of Dendritic Cell Apoptosis and CD8 + Cytotoxicity by Histamine: Role of Protein Kinase C. Mediators Inflamm 2017; 2017:9402814. [PMID: 28947859 PMCID: PMC5602510 DOI: 10.1155/2017/9402814] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 06/26/2017] [Accepted: 07/18/2017] [Indexed: 11/18/2022] Open
Abstract
Dendritic cells (DC) are able to present extracellular antigens associated with the molecules of the major histocompatibility complex class I. In a previous work, we demonstrated that the histamine (HIS), acting through H1/H4 receptors, increases the cross-presentation of soluble ovalbumin by murine DC and can enhance the recruitment of specific CD8+ T lymphocytes during the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying this enhancement. We showed that the cytotoxicity of specific CD8+ lymphocytes is increased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosome acidification. It is known that HIS acts through G protein-coupled receptors. The H1/H4 receptors are associated with a Gq subunit, which involves PKC signaling, a pathway related to the apoptotic process. Interestingly, we demonstrated for the first time that HIS prevents DC apoptosis induced by heat shock through the inhibition of caspase-3, a mechanism dependent on PKC activation, since it is reversed by its inhibition. By contrast, cytolytic activity of T lymphocytes induced by HIS-stimulated DC was independent of PKC pathway.
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Chae MR, Kang SJ, Lee KP, Choi BR, Kim HK, Park JK, Kim CY, Lee SW. Onion (Allium cepa L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel. Andrology 2017; 5:979-989. [PMID: 28805023 DOI: 10.1111/andr.12406] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Revised: 06/13/2017] [Accepted: 06/27/2017] [Indexed: 01/14/2023]
Abstract
Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 μg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 μm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.
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Affiliation(s)
- M R Chae
- Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S J Kang
- Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - K P Lee
- Laboratory of Physiology, College of Veterinary Medicine, Chungnam National University, Daejeon, Korea
| | - B R Choi
- Department of Urology, Medical School and Institute for Medical Sciences, Chonbuk National University, Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, Korea
| | - H K Kim
- College of Pharmacy, Kyungsung University, Busan, Korea
| | - J K Park
- Department of Urology, Medical School and Institute for Medical Sciences, Chonbuk National University, Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, Korea
| | - C Y Kim
- College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Korea
| | - S W Lee
- Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
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Zhu B, Yu L, Yue Q. Co-delivery of vincristine and quercetin by nanocarriers for lymphoma combination chemotherapy. Biomed Pharmacother 2017; 91:287-294. [PMID: 28463792 DOI: 10.1016/j.biopha.2017.02.112] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 02/09/2017] [Accepted: 02/15/2017] [Indexed: 12/18/2022] Open
Abstract
PURPOSE Chemotherapy is the current standard treatment for Non-Hodgkin's lymphoma (NHL). Combination therapy is emerging as an important strategy for a better long-term prognosis with decreased side effects, maximized therapeutic effect. The aim of this study is to deliver vincristine (VCR) and quercetin (QU) with synergistic drug ratios through lipid-polymeric nanocarriers (LPNs) for the lymphoma combination chemotherapy METHODS: In this present study, we constructed VCR and QU dual-loaded LPNs (VCR/QU LPNs) and investigated their antitumor efficacy in vitro cell culture models and a tumor xenograft mouse model. RESULTS The formulated VCR/QU LPNs exhibited nano-size, negative zeta potential with sustained release profile in vitro. The dual drug loaded LPNs exhibited the best antitumor efficacy in vitro and in vivo. CONCLUSION It could be concluded that VCR/QU LPNs can combine the efficiency of these two drugs, bring about synergistic effect. Co-encapsulation of VCR and QN in the same LPNs has potential as a novel therapeutic approach to overcome chemo-resistant lymphoma.
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Affiliation(s)
- Baomin Zhu
- Department of Blood Transfusion, Linyi People's Hospital, Linyi, Shandong, PR China
| | - Lianling Yu
- Department of Blood Transfusion, Linyi People's Hospital, Linyi, Shandong, PR China
| | - QingCai Yue
- Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong, PR China.
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Samsonowicz M, Regulska E. Spectroscopic study of molecular structure, antioxidant activity and biological effects of metal hydroxyflavonol complexes. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2017; 173:757-771. [PMID: 27792987 DOI: 10.1016/j.saa.2016.10.031] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 10/11/2016] [Accepted: 10/18/2016] [Indexed: 05/05/2023]
Abstract
Flavonols with varied hydroxyl substitution can act as strong antioxidants. Thanks to their ability to chelate metals as well as to donate hydrogen atoms they have capacity to scavenge free radicals. Their metal complexes are often more active in comparison with free ligands. They exhibit interesting biological properties, e.g. anticancer, antiphlogistic and antibacterial. The relationship between molecular structure and their biological properties was intensively studied using spectroscopic methods (UV-Vis, IR, Raman, NMR, ESI-MS). The aim of this paper is review on spectroscopic analyses of molecular structure and biological activity of hydroxyflavonol metal complexes.
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Affiliation(s)
- Mariola Samsonowicz
- Bialystok University of Technology, Division of Chemistry, Wiejska 45E, 15-351 Bialystok, Poland.
| | - Ewa Regulska
- Bialystok University of Technology, Division of Chemistry, Wiejska 45E, 15-351 Bialystok, Poland
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Maurya AK, Vinayak M. Quercetin Attenuates Cell Survival, Inflammation, and Angiogenesis via Modulation of AKT Signaling in Murine T-Cell Lymphoma. Nutr Cancer 2017; 69:470-480. [PMID: 28107044 DOI: 10.1080/01635581.2017.1267775] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice. Protein level was determined by Western blotting. Nitric oxide (NO) level was estimated spectrophotometrically using Griess reagent. Results show downregulation in phosphorylation of AKT and PDK1 by quercetin, which was consistent with decreased phosphorylation of downstream survival factors such as BAD, GSK-3β, mTOR, and IkBα. Further, quercetin attenuated the levels of angiogenic factor VEGF-A and inflammatory enzymes COX-2 and iNOS as well as NO levels, whereas it increased the levels of phosphatase PTEN. Overall results suggest that quercetin modulates AKT signaling leading to attenuation of cell survival, inflammation, and angiogenesis in lymphoma-bearing mice.
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Affiliation(s)
- Akhilendra Kumar Maurya
- a Laboratory of Biochemistry and Molecular Biology , Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University , Varanasi , India
| | - Manjula Vinayak
- a Laboratory of Biochemistry and Molecular Biology , Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University , Varanasi , India
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Yadav MK, Maurya AK, Rajput G, Manar KK, Vinayak M, Drew MGB, Singh N. New planar trans-copper(II) β-dithioester chelate complexes: synthesis, characterization, anticancer activity and DNA-binding/cleavage studies. J COORD CHEM 2017. [DOI: 10.1080/00958972.2016.1275589] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Manoj Kumar Yadav
- Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Akhilendra Kumar Maurya
- Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Gunjan Rajput
- Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Krishna Kumar Manar
- Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Manjula Vinayak
- Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
| | | | - Nanhai Singh
- Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, India
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Wang W, Sun C, Mao L, Ma P, Liu F, Yang J, Gao Y. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends Food Sci Technol 2016. [DOI: 10.1016/j.tifs.2016.07.004] [Citation(s) in RCA: 364] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Maurya AK, Vinayak M. PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma. Leuk Lymphoma 2016; 58:1153-1161. [PMID: 27658642 DOI: 10.1080/10428194.2016.1225207] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Aberrant activation of PI3K-AKT signaling in many pathological conditions including cancer has attracted much of interest for drug targeting. Various isoforms are known from three classes of PI3K. Targeting selective isoform is advantageous to overcome the global deleterious effects of drug. PI-103 is a specific inhibitor of p110α of class I PI3K. The present study is aimed to analyze anti-carcinogenic activity of PI-103 in Dalton's lymphoma ascite (DLA) cells. Result shows regression in cell proliferation and increased apoptosis in terms of increased Annexin V binding, nuclear fragmentation and active caspase 3 level. It is correlated with attenuation of PI3K-AKT signaling by PI-103 via downregulation of the level of p110α, phospho-p85α, phospho- AKT, and PKCα in DLA cells as well as in H2O2 induced DLA cells. Additionally, ROS accumulation is declined in H2O2 induced DLA cells. Overall result suggests that PI-103 attenuates PI3K-AKT signaling via induction of apoptosis in murine T-cell lymphoma.
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Affiliation(s)
- Akhilendra Kumar Maurya
- a Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science , Banaras Hindu University , Varanasi , India
| | - Manjula Vinayak
- a Biochemistry & Molecular Biology Laboratory, Department of Zoology, Institute of Science , Banaras Hindu University , Varanasi , India
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Pandey RP, Parajuli P, Koffas MA, Sohng JK. Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology. Biotechnol Adv 2016; 34:634-662. [DOI: 10.1016/j.biotechadv.2016.02.012] [Citation(s) in RCA: 167] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 02/24/2016] [Accepted: 02/29/2016] [Indexed: 12/18/2022]
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Maurya AK, Vinayak M. PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide. PLoS One 2016; 11:e0160686. [PMID: 27494022 PMCID: PMC4975451 DOI: 10.1371/journal.pone.0160686] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Accepted: 07/24/2016] [Indexed: 12/15/2022] Open
Abstract
Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS) has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton's lymphoma ascite (DLA) cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism.
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Affiliation(s)
- Akhilendra Kumar Maurya
- Biochemistry & Molecular Biology Laboratory, Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, India
| | - Manjula Vinayak
- Biochemistry & Molecular Biology Laboratory, Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, India
- * E-mail:
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Das J, Ramani R, Suraju MO. Polyphenol compounds and PKC signaling. Biochim Biophys Acta Gen Subj 2016; 1860:2107-21. [PMID: 27369735 DOI: 10.1016/j.bbagen.2016.06.022] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 06/01/2016] [Accepted: 06/26/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Naturally occurring polyphenols found in food sources provide huge health benefits. Several polyphenolic compounds are implicated in the prevention of disease states, such as cancer. One of the mechanisms by which polyphenols exert their biological actions is by interfering in the protein kinase C (PKC) signaling pathways. PKC belongs to a superfamily of serine-threonine kinase and are primarily involved in phosphorylation of target proteins controlling activation and inhibition of many cellular processes directly or indirectly. SCOPE OF REVIEW Despite the availability of substantial literature data on polyphenols' regulation of PKC, no comprehensive review article is currently available on this subject. This article reviews PKC-polyphenol interactions and its relevance to various disease states. In particular, salient features of polyphenols, PKC, interactions of naturally occurring polyphenols with PKC, and future perspective of research on this subject are discussed. MAJOR CONCLUSIONS Some polyphenols exert their antioxidant properties by regulating the transcription of the antioxidant enzyme genes through PKC signaling. Regulation of PKC by polyphenols is isoform dependent. The activation or inhibition of PKC by polyphenols has been found to be dependent on the presence of membrane, Ca(2+) ion, cofactors, cell and tissue types etc. Two polyphenols, curcumin and resveratrol are in clinical trials for the treatment of colon cancer. GENERAL SIGNIFICANCE The fact that 74% of the cancer drugs are derived from natural sources, naturally occurring polyphenols or its simple analogs with improved bioavailability may have the potential to be cancer drugs in the future.
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Affiliation(s)
- Joydip Das
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, United States.
| | - Rashmi Ramani
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, United States
| | - M Olufemi Suraju
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, United States
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Rivera Rivera A, Castillo-Pichardo L, Gerena Y, Dharmawardhane S. Anti-Breast Cancer Potential of Quercetin via the Akt/AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Cascade. PLoS One 2016; 11:e0157251. [PMID: 27285995 PMCID: PMC4902235 DOI: 10.1371/journal.pone.0157251] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 05/26/2016] [Indexed: 12/25/2022] Open
Abstract
The Akt/adenosine monophosphate protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway has emerged as a critical signaling nexus for regulating cellular metabolism, energy homeostasis, and cell growth. Thus, dysregulation of this pathway contributes to the development of metabolic disorders such as obesity, type 2diabetes, and cancer. We previously reported that a combination of grape polyphenols (resveratrol, quercetin and catechin: RQC), at equimolar concentrations, reduces breast cancer (BC) growth and metastasis in nude mice, and inhibits Akt and mTOR activities and activates AMPK, an endogenous inhibitor of mTOR, in metastatic BC cells. The objective of the present study was to determine the contribution of individual polyphenols to the effect of combined RQC on mTOR signaling. Metastatic BC cells were treated with RQC individually or in combination, at various concentrations, and the activities (phosphorylation) of AMPK, Akt, and the mTOR downstream effectors, p70S6 kinase (p70S6K) and 4E binding protein (4EBP1), were determined by Western blot. Results show that quercetin was the most effective compound for Akt/mTOR inhibition. Treatment with quercetin at 15μM had a similar effect as the RQC combination in the inhibition of BC cell proliferation, apoptosis, and migration. However, cell cycle analysis showed that the RQC treatment arrested BC cells in the G1 phase, while quercetin arrested the cell cycle in G2/M. In vivo experiments, using SCID mice with implanted tumors from metastatic BC cells, demonstrated that administration of quercetin at 15mg/kg body weight resulted in a ~70% reduction in tumor growth. In conclusion, quercetin appears to be a viable grape polyphenol for future development as an anti BC therapeutic.
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Affiliation(s)
- Amilcar Rivera Rivera
- Department of Biochemistry, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Linette Castillo-Pichardo
- Department of Biochemistry, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
- Department of Pathology and Laboratory Medicine, Universidad Central del Caribe, Bayamón, Puerto Rico
| | - Yamil Gerena
- Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Suranganie Dharmawardhane
- Department of Biochemistry, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
- * E-mail:
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Nam JS, Sharma AR, Nguyen LT, Chakraborty C, Sharma G, Lee SS. Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine. Molecules 2016; 21:E108. [PMID: 26797598 PMCID: PMC6273093 DOI: 10.3390/molecules21010108] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 12/24/2015] [Accepted: 01/07/2016] [Indexed: 12/31/2022] Open
Abstract
Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. Quercetin is known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, quercetin possesses great medicinal value, its applications as a therapeutic drug are limited. Problems like low oral bioavailability and poor aqueous solubility make quercetin an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of quercetin is also a major barrier for its clinical translation. Hence, to overcome these disadvantages quercetin-based nanoformulations are being considered in recent times. Nanoformulations of quercetin have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to summarize various methods utilized for nanofabrication of quercetin formulations and for stable and sustained delivery of quercetin. We have also highlighted the various desirable measures for its use as a promising onco-therapeutic agent.
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Affiliation(s)
- Ju-Suk Nam
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Korea.
| | - Ashish Ranjan Sharma
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Korea.
| | - Lich Thi Nguyen
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Korea.
| | - Chiranjib Chakraborty
- Department of Bio-informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida 203201, India.
| | - Garima Sharma
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Korea.
- Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh 201313, India.
| | - Sang-Soo Lee
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 200704, Korea.
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Smith AJ, Oertle J, Warren D, Prato D. Quercetin: A Promising Flavonoid with a Dynamic Ability to Treat Various Diseases, Infections, and Cancers. ACTA ACUST UNITED AC 2016. [DOI: 10.4236/jct.2016.72010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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D'Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia 2015; 106:256-71. [PMID: 26393898 DOI: 10.1016/j.fitote.2015.09.018] [Citation(s) in RCA: 479] [Impact Index Per Article: 47.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/16/2015] [Accepted: 09/18/2015] [Indexed: 12/17/2022]
Abstract
Great interest is currently centered on the biologic activities of quercetin a polyphenol belonging to the class of flavonoids, natural products well known for their beneficial effects on health, long before their biochemical characterization. In particular, quercetin is categorized as a flavonol, one of the five subclasses of flavonoid compounds. Although flavonoids occur as either glycosides (with attached glycosyl groups) or as aglycones, most altogether of the dietary intake concerning quercetin is in the glycoside form. Following chewing, digestion, and absorption sugar moieties can be released from quercetin glycosides. Several organs contribute to quercetin metabolism, including the small intestine, the kidneys, the large intestine, and the liver, giving rise to glucuronidated, methylated, and sulfated forms of quercetin; moreover, free quercetin (such as aglycone) is also found in plasma. Quercetin is now largely utilized as a nutritional supplement and as a phytochemical remedy for a variety of diseases like diabetes/obesity and circulatory dysfunction, including inflammation as well as mood disorders. Owing to its basic chemical structure themost obvious feature of quercetin is its strong antioxidant activity which potentially enables it to quench free radicals from forming resonance-stabilized phenoxyl radicals. In this review the molecular, cellular, and functional bases of therapy will be emphasized taking strictly into account data appearing in the peer-reviewed literature and summarizing the main therapeutic applications of quercetin; furthermore, the drug metabolism and the main drug interaction as well as the potential toxicity will be also spotlighted.
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Affiliation(s)
- Gabriele D'Andrea
- University of L'Aquila, Dept. of Biotechnological and Applied Clinical Sciences, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
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