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1
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Attar ES, Chaudhari VH, Deokar CG, Dyawanapelly S, Devarajan PV. Nano Drug Delivery Strategies for an Oral Bioenhanced Quercetin Formulation. Eur J Drug Metab Pharmacokinet 2023; 48:495-514. [PMID: 37523008 DOI: 10.1007/s13318-023-00843-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2023] [Indexed: 08/01/2023]
Abstract
Quercetin, a naturally occurring flavonoid, has been credited with a wide spectrum of therapeutic properties. However, the oral use of quercetin is limited due to its poor water solubility, low bioavailability, rapid metabolism, and rapid plasma clearance. Quercetin has been studied extensively when used with various nanodelivery systems for enhancing quercetin bioavailability. To enhance its oral bioavailability and efficacy, various quercetin-loaded nanosystems such as nanosuspensions, polymer nanoparticles, metal nanoparticles, emulsions, liposomes or phytosomes, micelles, solid lipid nanoparticles, and other lipid-based nanoparticles have been investigated in in-vitro cells, in-vivo animal models, and humans. Among the aforementioned nanosystems, quercetin phytosomes are attracting more interest and are available on the market. The present review covers insights into the possibilities of harnessing quercetin for several therapeutic applications and a special focus on anticancer applications and the clinical benefits of nanoquercetin formulations.
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Affiliation(s)
- Esha S Attar
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, Maharashtra, 400019, India
| | - Vanashree H Chaudhari
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, Maharashtra, 400019, India
| | - Chaitanya G Deokar
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, Maharashtra, 400019, India
| | - Sathish Dyawanapelly
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, Maharashtra, 400019, India
| | - Padma V Devarajan
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, Maharashtra, 400019, India.
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2
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Lotfi N, Yousefi Z, Golabi M, Khalilian P, Ghezelbash B, Montazeri M, Shams MH, Baghbadorani PZ, Eskandari N. The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update. Front Immunol 2023; 14:1077531. [PMID: 36926328 PMCID: PMC10011078 DOI: 10.3389/fimmu.2023.1077531] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 02/07/2023] [Indexed: 03/08/2023] Open
Abstract
Cancer is caused by abnormal proliferation of cells and aberrant recognition of the immune system. According to recent studies, natural products are most likely to be effective at preventing cancer without causing any noticeable complications. Among the bioactive flavonoids found in fruits and vegetables, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties. This review aims to highlight the potential therapeutic effects of quercetin on some different types of cancers including blood, lung and prostate cancers.
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Affiliation(s)
- Noushin Lotfi
- Department of Medical Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Yousefi
- School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Marjan Golabi
- Department of Medical Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parvin Khalilian
- Department of Medical Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Behrooz Ghezelbash
- Department of Medical Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Montazeri
- Department of Medical Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Hossein Shams
- Department of Medical Immunology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | | | - Nahid Eskandari
- Department of Medical Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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3
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Bonuccelli G, Sotgia F, Lisanti MP. Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation. Aging (Albany NY) 2022; 14:9466-9483. [PMID: 36455875 PMCID: PMC9792210 DOI: 10.18632/aging.204412] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/17/2022] [Indexed: 12/05/2022]
Abstract
Here, we report the identification of key compounds that effectively inhibit the anchorage-independent growth and propagation of cancer stem cells (CSCs), as determined via screening using MCF7 cells, a human breast adenocarcinoma cell line. More specifically, we employed the mammosphere assay as an experimental format, which involves the generation of 3D spheroid cultures, using low-attachment plates. These positive hit compounds can be divided into 5 categories: 1) dietary supplements (quercetin and glucosamine); 2) FDA-approved drugs (carvedilol and ciprofloxacin); 3) natural products (aloe emodin, aloin, tannic acid, chlorophyllin copper salt, azelaic acid and adipic acid); 4) flavours (citral and limonene); and 5) vitamins (nicotinamide and nicotinic acid). In addition, for the compounds quercetin, glucosamine and carvedilol, we further assessed their metabolic action, using the Seahorse to conduct metabolic flux analysis. Our results indicate that these treatments can affect glycolytic flux and suppress oxidative mitochondrial metabolism (OXPHOS). Therefore, quercetin, glucosamine and carvedilol can reprogram the metabolic phenotype of breast cancer cells. Despite having diverse chemical structures, these compounds all interfere with mitochondrial metabolism. As these compounds halt CSCs propagation, ultimately, they may have therapeutic potential.
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Affiliation(s)
- Gloria Bonuccelli
- Translational Medicine, School of Science, Engineering and Environment, Biomedical Research Centre, University of Salford, Greater Manchester, United Kingdom
| | - Federica Sotgia
- Translational Medicine, School of Science, Engineering and Environment, Biomedical Research Centre, University of Salford, Greater Manchester, United Kingdom
| | - Michael P. Lisanti
- Translational Medicine, School of Science, Engineering and Environment, Biomedical Research Centre, University of Salford, Greater Manchester, United Kingdom
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Mahmod AI, Haif SK, Kamal A, Al-Ataby IA, Talib WH. Chemoprevention effect of the Mediterranean diet on colorectal cancer: Current studies and future prospects. Front Nutr 2022; 9:924192. [PMID: 35990343 PMCID: PMC9386380 DOI: 10.3389/fnut.2022.924192] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 07/18/2022] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most deadly cancer worldwide. Nevertheless, more than 70% of CRC cases are resulted from sporadic tumorigenesis and are not inherited. Since adenoma-carcinoma development is a slow process and may take up to 20 years, diet-based chemoprevention could be an effective approach in sporadic CRC. The Mediterranean diet is an example of a healthy diet pattern that consists of a combination of nutraceuticals that prevent several chronic diseases and cancer. Many epidemiological studies have shown the correlation between adherence to the Mediterranean diet and low incidence of CRC. The goal of this review is to shed the light on the anti-inflammatory and anti-colorectal cancer potentials of the natural bioactive compounds derived from the main foods in the Mediterranean diet.
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Affiliation(s)
- Asma Ismail Mahmod
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Shatha Khaled Haif
- Department of Pharmacy, Princess Sarvath Community College, Amman, Jordan
| | - Ayah Kamal
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Israa A Al-Ataby
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Wamidh H Talib
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
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5
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Rangel VM, Gu L, Chen G, Chen QH, Xue L. 5-Substituted 3, 3', 4', 7-tetramethoxyflavonoids - A novel class of potent DNA triplex specific binding ligands. Bioorg Med Chem Lett 2022; 61:128608. [PMID: 35143982 DOI: 10.1016/j.bmcl.2022.128608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/01/2022] [Accepted: 02/02/2022] [Indexed: 11/18/2022]
Abstract
Herein, we present a class of potent triplex DNA binding ligands derived from the natural product quercetin, which is the first of its kind that has ever been reported in the literature. The binding of 5-substituted quercetin derivatives (3, 3', 4', 7-tetramethoxyflavonoids) to triplex and duplex DNA was investigated using several biophysical tools, including thermal denaturation monitored by UV, circular dichroism, differential scanning calorimetry, and isothermal titration calorimetry. Experimental data reveal that several 5-substituted 3, 3', 4', 7-tetramethoxyflavonoids have remarkable effects on binding to DNA triple helices, and they do not influence the double-helical DNA structures. A few derivatives such as compounds 5 and 7 have comparable (if not better) binding affinities to neomycin, a well-known DNA triplex binding ligand, under the same conditions. The amino-containing side chains at the 5-position of 3, 3', 4', 7-tetramethoxyflavonoids are crucial for the observed binding affinity and specificity.
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Affiliation(s)
- Vanessa M Rangel
- Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA
| | - Landy Gu
- Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA
| | - Guanglin Chen
- Department of Chemistry, California State University, Fresno, CA 93740, USA
| | - Qiao-Hong Chen
- Department of Chemistry, California State University, Fresno, CA 93740, USA
| | - Liang Xue
- Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
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6
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Experimental studies and computational modeling on cytochrome c reduction by quercetin: The role of oxidability and binding affinity. J Mol Struct 2021. [DOI: 10.1016/j.molstruc.2021.130995] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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7
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Beigoli S, Behrouz S, Memarzia A, Ghasemi SZ, Boskabady M, Marefati N, Kianian F, Khazdair MR, El-Seedi H, Boskabady MH. Effects of Allium cepa and Its Constituents on Respiratory and Allergic Disorders: A Comprehensive Review of Experimental and Clinical Evidence. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:5554259. [PMID: 34552650 PMCID: PMC8452398 DOI: 10.1155/2021/5554259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/10/2021] [Accepted: 08/30/2021] [Indexed: 11/27/2022]
Abstract
The health benefits of Allium cepa (A. cepa) have been proclaimed for centuries. Various pharmacological and therapeutic effects on respiratory, allergic, and immunologic disorders are shown by A. cepa and its constituents. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are the main compounds of the plant. A. cepa displays broad-spectrum pharmacological activities including antioxidant, anti-inflammatory, antihypertensive, and antidiabetic effects. Our objective in this review is to present the effects of A. cepa and its constituents on respiratory, allergic, and immunologic disorders. Different online databases were searched to find articles related to the effect of A. cepa extracts and its constituents on respiratory, allergic, and immunologic disorders until the end of December 2020 using keywords such as onion, A. cepa, constituents of A. cepa, therapeutic effects and pharmacological effects, and respiratory, allergic, and immunologic disorders. Extracts and constituents of A. cepa showed tracheal smooth muscle relaxant effects, indicating possible bronchodilator activities or relieving effects on obstructive respiratory diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of A. cepa was induced by their antioxidant, immunomodulatory, and anti-inflammatory effects. The preventive effects of the plant and its components on lung disorders induced by exposure to noxious agents as well as lung cancer, lung infection, and allergic and immunologic disorders were also indicated in the experimental and clinical studies. Therefore, this review may be considered a scientific basis for development of therapies using this plant, to improve respiratory, allergic, and immunologic disorders.
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Affiliation(s)
- Sima Beigoli
- Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sepideh Behrouz
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arghavan Memarzia
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyyedeh Zahra Ghasemi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Marzie Boskabady
- Dental Materials Research Center and Department of Pediatric Dentistry, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pediatric Dentistry, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Narges Marefati
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farzaneh Kianian
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Khazdair
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Hesham El-Seedi
- Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23, Uppsala, Sweden
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
- Al-Rayan Research and Innovation Center, Al-Rayan Colleges, Medina 42541, Saudi Arabia
| | - Mohammad Hosein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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8
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Advantageous/Unfavorable Effect of Quercetin on the Membranes of SK-N-SH Neuroblastoma Cells. Molecules 2021; 26:molecules26164945. [PMID: 34443533 PMCID: PMC8397999 DOI: 10.3390/molecules26164945] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/11/2021] [Accepted: 08/12/2021] [Indexed: 11/27/2022] Open
Abstract
Quercetin is a polyphenolic compound, the effects of which raise scientists’ doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).
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9
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Nile A, Nile SH, Cespedes-Acuña CL, Oh JW. Spiraeoside extracted from red onion skin ameliorates apoptosis and exerts potent antitumor, antioxidant and enzyme inhibitory effects. Food Chem Toxicol 2021; 154:112327. [PMID: 34116102 DOI: 10.1016/j.fct.2021.112327] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/18/2021] [Accepted: 06/04/2021] [Indexed: 12/11/2022]
Abstract
Red onion skin waste (ROSW) was analyzed for extraction of naturally occurring 4'-O-glucoside of quercetin, spiraeoside (SPI) with promising biological activities. Reversed-phase high-performance liquid chromatography was used to determine the SPI content in three different solvent extracts of ROSW: water (12.2 mg/g), methanol (27.6 mg/g), and ethanol (32.5 mg/g). The ethanol extract and SPI showed significant radical-scavenging and anti-inflammatory activities. In addition, the anti-cancer effects of SPI on a HeLa cells was investigated. The results indicated that SPI treatment significantly inhibited cell growth, and the dose of 50 μg/mL exhibited the highest anti-cancer activity. SPI inhibited the expression of B-cell lymphoma 2 and BH3-interacting domain-death agonist and promoted apoptosis by activating caspase-9/-3 expression. Notably, SPI inhibited the expression of mu-2-related death-inducing gene, a molecule involved in death receptor-mediated apoptotic signaling. Cyclin-dependent kinase 2-cyclin-E expression was also inhibited after SPI treatment, particularly at the G2/M checkpoint. Our findings provide novel insights into the apoptotic potential with promising anticancer and enzyme inhibitory effects of ROSW SPI.
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Affiliation(s)
- Arti Nile
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
| | - Shivraj Hariram Nile
- Laboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China.
| | - Carlos L Cespedes-Acuña
- Laboratory of Phytochemistry and Eco-toxicology, Research Group in Chemistry and Biotechnology of Bioactive Natural Products, Department of Basic Sciences, Faculty of Sciences, University of Bio-Bío, Andrés Bello Avenue # 720, Chillan, Chile
| | - Jae-Wook Oh
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
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Harish BS, Raja MRC, Mahapatra SK, Uppuluri KB. Production Enhancement of an Anticoagulant Trypsin Inhibitor from Oceanimonas sp. BPMS22 and Its Anti-cancer Activity. Int J Pept Res Ther 2021. [DOI: 10.1007/s10989-020-10078-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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11
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Szejk-Arendt M, Czubak-Prowizor K, Macieja A, Poplawski T, Olejnik AK, Pawlaczyk-Graja I, Gancarz R, Zbikowska HM. Polyphenolic-polysaccharide conjugates from medicinal plants of Rosaceae/Asteraceae family protect human lymphocytes but not myeloid leukemia K562 cells against radiation-induced death. Int J Biol Macromol 2020; 156:1445-1454. [DOI: 10.1016/j.ijbiomac.2019.11.186] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 11/14/2019] [Accepted: 11/21/2019] [Indexed: 01/21/2023]
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12
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Brisdelli F, Di Francesco L, Giorgi A, Lizzi AR, Luzi C, Mignogna G, Bozzi A, Schininà ME. Proteomic Analysis of Quercetin-Treated K562 Cells. Int J Mol Sci 2019; 21:ijms21010032. [PMID: 31861640 PMCID: PMC6981597 DOI: 10.3390/ijms21010032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 12/17/2019] [Indexed: 02/07/2023] Open
Abstract
Among natural products under investigation for their additive potential in cancer prevention and treatment, the flavonoid quercetin has received attention for its effects on the cell cycle arrest and apoptosis. In the past, we addressed this issue in K562 cells, a cellular model of the human chronic myeloid leukemia. Here, we applied stable isotope labeling by amino acids in cell culture (SILAC) proteomics with the aim to increase knowledge on the regulative and metabolic pathways modulated by quercetin in these cells. After 24 h of quercetin treatment, we observed that apoptosis was not completely established, thus we selected this time range to capture quantitative data. As a result, we were able to achieve a robust identification of 1703 proteins, and to measure fold changes between quercetin-treated and untreated cells for 1206 proteins. Through a bioinformatics functional analysis on a subset of 112 proteins, we propose that the apoptotic phenotype of K562 cells entails a significant modulation of the translational machinery, RNA metabolism, antioxidant defense systems, and enzymes involved in lipid metabolism. Finally, we selected eight differentially expressed proteins, validated their modulated expression in quercetin-treated K562 cells, and discussed their possible role in flavonoid cytotoxicity. This quantitative profiling, performed for the first time on this type of tumor cells upon treatment with a flavonoid, will contribute to revealing the molecular basis of the multiplicity of the effects selectively exerted by quercetin on K562 cells.
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Affiliation(s)
- Fabrizia Brisdelli
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (F.B.); (A.R.L.); (C.L.); (A.B.)
| | - Laura Di Francesco
- Department of Biochemical Sciences, Sapienza, University of Rome, 00185 Rome, Italy; (L.D.F.); (A.G.); (G.M.)
| | - Alessandra Giorgi
- Department of Biochemical Sciences, Sapienza, University of Rome, 00185 Rome, Italy; (L.D.F.); (A.G.); (G.M.)
| | - Anna Rita Lizzi
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (F.B.); (A.R.L.); (C.L.); (A.B.)
| | - Carla Luzi
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (F.B.); (A.R.L.); (C.L.); (A.B.)
| | - Giuseppina Mignogna
- Department of Biochemical Sciences, Sapienza, University of Rome, 00185 Rome, Italy; (L.D.F.); (A.G.); (G.M.)
| | - Argante Bozzi
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (F.B.); (A.R.L.); (C.L.); (A.B.)
| | - M. Eugenia Schininà
- Department of Biochemical Sciences, Sapienza, University of Rome, 00185 Rome, Italy; (L.D.F.); (A.G.); (G.M.)
- Correspondence:
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13
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Teixeira J, Chavarria D, Borges F, Wojtczak L, Wieckowski MR, Karkucinska-Wieckowska A, Oliveira PJ. Dietary Polyphenols and Mitochondrial Function: Role in Health and Disease. Curr Med Chem 2019; 26:3376-3406. [PMID: 28554320 DOI: 10.2174/0929867324666170529101810] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 04/23/2017] [Accepted: 04/23/2017] [Indexed: 12/12/2022]
Abstract
Mitochondria are cytoplasmic double-membraned organelles that are involved in a myriad of key cellular regulatory processes. The loss of mitochondrial function is related to the pathogenesis of several human diseases. Over the last decades, an increasing number of studies have shown that dietary polyphenols can regulate mitochondrial redox status, and in some cases, prevent or delay disease progression. This paper aims to review the role of four dietary polyphenols - resveratrol, curcumin, epigallocatechin-3-gallate nd quercetin - in molecular pathways regulated by mitochondria and their potential impact on human health. Cumulative evidence showed that the aforementioned polyphenols improve mitochondrial functions in different in vitro and in vivo experiments. The mechanisms underlying the polyphenols' beneficial effects include, among others, the attenuation of oxidative stress, the regulation of mitochondrial metabolism and biogenesis and the modulation of cell-death signaling cascades, among other mitochondrial-independent effects. The understanding of the chemicalbiological interactions of dietary polyphenols, namely with mitochondria, may have a huge impact on the treatment of mitochondrial dysfunction-related disorders.
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Affiliation(s)
- José Teixeira
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169- 007, Portugal.,CNC - Center for Neuroscience and Cell Biology, UC-Biotech, Biocant Park - Cantanhede, University of Coimbra, Portugal
| | - Daniel Chavarria
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169- 007, Portugal
| | - Fernanda Borges
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4169- 007, Portugal
| | - Lech Wojtczak
- Nencki Institute of Experimental Biology, Warsaw, Poland
| | | | | | - Paulo J Oliveira
- CNC - Center for Neuroscience and Cell Biology, UC-Biotech, Biocant Park - Cantanhede, University of Coimbra, Portugal
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14
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Rubio V, García-Pérez AI, Herráez A, Diez JC. Different roles of Nrf2 and NFKB in the antioxidant imbalance produced by esculetin or quercetin on NB4 leukemia cells. Chem Biol Interact 2018; 294:158-166. [PMID: 30171828 DOI: 10.1016/j.cbi.2018.08.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/23/2018] [Accepted: 08/17/2018] [Indexed: 01/08/2023]
Abstract
Esculetin (6,7-dihydrocoumarin) and the flavonoid quercetin (3,5,7,3',4' pentahydroxyflavone) are compounds that could change the balance of redox homeostasis. NB4 leukemia cells were treated with 25 μM quercetin for 24 h and with esculetin at either 100 or 500 μM for different times. Quercetin increased the levels of pro-inflammatory NFkB p65 in the nucleus correspondingly reducing them in the cytosol. The levels of NFkB p65 decreased in the nucleus at high esculetin concentration treatments for long times (19 h), concomitantly increasing the levels of anti-inflammatory NFkB p50 in the nucleus. This could suggest formation of inhibitory p50 homodimers possibly related with anti-inflammatory response. Lipoxygenase expression was reduced either by esculetin or quercetin. A significant increase of Nrf2 in the nucleus of NB4 cells treated with 100 μM esculetin for 19 h was observed. Quercetin increased the levels of Nrf2 in the cytosol reducing them in the nucleus. Superoxide dismutase expression increased in NB4 cells treated with esculetin in contrast with quercetin. All these data support a relevant differential role for NFkB and Nrf2 in anti-inflammatory and redox response when apoptosis was induced by esculetin or quercetin in human leukemia NB4 cells.
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Affiliation(s)
- Virginia Rubio
- Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain
| | - Ana I García-Pérez
- Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain
| | - Angel Herráez
- Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain
| | - José C Diez
- Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.
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15
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Sak K, Everaus H. Established Human Cell Lines as Models to Study Anti-leukemic Effects of Flavonoids. Curr Genomics 2017; 18:3-26. [PMID: 28503087 PMCID: PMC5321770 DOI: 10.2174/1389202917666160803165447] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 11/20/2015] [Accepted: 11/27/2015] [Indexed: 12/19/2022] Open
Abstract
Despite the extensive work on pathological mechanisms and some recent advances in the treatment of different hematological malignancies, leukemia continues to present a significant challenge being frequently considered as incurable disease. Therefore, the development of novel therapeutic agents with high efficacy and low toxicity is urgently needed to improve the overall survival rate of patients. In this comprehensive review article, the current knowledge about the anticancer activities of flavonoids as plant secondary polyphenolic metabolites in the most commonly used human established leukemia cell lines (HL-60, NB4, KG1a, U937, THP-1, K562, Jurkat, CCRF- CEM, MOLT-3, and MOLT-4) is compiled, revealing clear anti-proliferative, pro-apoptotic, cell cycle arresting, and differentiation inducing effects for certain compounds. Considering the low toxicity of these substances in normal blood cells, the presented data show a great potential of flavonoids to be developed into novel anti-leukemia agents applicable also in the malignant cells resistant to the current conventional chemotherapeutic drugs.
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Affiliation(s)
- Katrin Sak
- Department of Hematology and Oncology, University of Tartu, Tartu, Estonia
| | - Hele Everaus
- Department of Hematology and Oncology, University of Tartu, Tartu, Estonia
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16
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Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, Choudhary B, Raghavan SC. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis. Sci Rep 2016; 6:24049. [PMID: 27068577 PMCID: PMC4828642 DOI: 10.1038/srep24049] [Citation(s) in RCA: 310] [Impact Index Per Article: 34.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 03/17/2016] [Indexed: 12/21/2022] Open
Abstract
Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy.
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Affiliation(s)
- Shikha Srivastava
- Department of Biochemistry, Indian Institute of Science, Bangalore-560 012, India
| | | | - Mahesh Hegde
- Department of Biochemistry, Indian Institute of Science, Bangalore-560 012, India
| | | | - Satish Kumar Tadi
- Department of Biochemistry, Indian Institute of Science, Bangalore-560 012, India
| | - Mrinal Srivastava
- Department of Biochemistry, Indian Institute of Science, Bangalore-560 012, India
| | - Bibha Choudhary
- Institute of Bioinformatics and Applied Biotechnology, Electronics City, Bangalore 560 100, India
| | - Sathees C Raghavan
- Department of Biochemistry, Indian Institute of Science, Bangalore-560 012, India
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17
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Fan J, Wang P, Wang X, Tang W, Liu C, Wang Y, Yuan W, Kong L, Liu Q. Induction of Mitochondrial Dependent Apoptosis in Human Leukemia K562 Cells by Meconopsis integrifolia: A Species from Traditional Tibetan Medicine. Molecules 2015; 20:11981-93. [PMID: 26133762 PMCID: PMC6332253 DOI: 10.3390/molecules200711981] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Revised: 05/15/2015] [Accepted: 05/18/2015] [Indexed: 12/14/2022] Open
Abstract
Objectives: Meconopsis integrifolia (M. integrifolia) is one of the most popular members in Traditional Tibetan Medicine. This study aimed to investigate the anticancer effect of M. integrifolia and to detect the underlying mechanisms of these effects. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and trypan blue assay were used to evaluate the cytotoxicity of M. integrifolia. Changes in cell nuclear morphology and reactive oxygen species (ROS) level were observed by fluorescent microscopy. Apoptosis ratio, DNA damage and mitochondrial membrane potential (MMP) loss were analyzed by flow cytometry. Western blotting assay was adopted to detect the proteins related to apoptosis. Immunofluorescence was used to observe the release of cytochrome C. Results: The obtained data revealed that M. integrifolia could significantly inhibit K562 cell viability, mainly by targeting apoptosis induction and cell cycle arrest in G2/M phase. Collapse in cell morphology, chromatin condensation, DNA damage and ROS accumulation were observed. Further mechanism detection revealed that mitochondrion might be a key factor in M. integrifolia-induced apoptosis. Conclusions: M. integrifolia could induce mitochondria mediated apoptosis and cell cycle arrest in G2/M phase with little damage to normal cells, suggesting that M. integrifolia might be a potential and efficient anticancer agent that deserves further investigation.
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Affiliation(s)
- Jianping Fan
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
- College of Life Sciences, Qinghai Normal University, No.38, West Wusi Road, 810008 Xining, China.
| | - Pan Wang
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Xiaobing Wang
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Wei Tang
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Chunliang Liu
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Yaqin Wang
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Wenjuan Yuan
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Lulu Kong
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
| | - Quanhong Liu
- Co-Innovation Center for Qinba Regions' Sustainable Development, College of Life Sciences, Shaanxi Normal University, No. 620, West Chang'an Avenue, Chang'an District, 710119 Xi'an, China.
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Carnicelli V, Lizzi AR, Gualtieri G, Bozzi A, Franceschini N, Di Giulio A. Effects of azidothymidine on protein kinase C activity and expression in erythroleukemic cell K562 and acute lymphoblastic leukemia cell HSB-2. Acta Biochim Biophys Sin (Shanghai) 2015; 47:278-84. [PMID: 25693686 DOI: 10.1093/abbs/gmv003] [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] [Indexed: 11/13/2022] Open
Abstract
Azidothymidine (AZT) is one of the anti-retroviral drugs currently used for the treatment of HIV-infected patients. Several other effects of the drug have been studied in vitro, such as the alterations of some enzymes, the inhibition of cell proliferation, and the increase of transferrin receptor expression. In this study, we investigated the alterations of protein kinase C (PKC) activity, PKCα and PKCβII expressions and plasmatic membrane fluidity induced by AZT in two cancer cell lines, human chronic myeloid (K562) and human acute lymphoblastic (HSB-2) leukemia cells, respectively. The results showed that both PKC activity and membrane fluidity in HSB-2 cells increased after 24 h of drug incubation. PKCα expression in HSB-2 cells decreased after 48 h of AZT exposure, when the cell growth also decreased. However, in K562 cells, the PKCα and PKCβII expressions enhanced in the presence of the drug when the growth was inhibited. The results indicate that AZT is less effective in inhibiting the growth of acute lymphoblastic HSB-2 leukemia cells than inhibiting that of chronic myeloid K562 cells. In fact, after 24 h exposure, the HSB-2 cell growth decreased less than K562 cell growth.
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Affiliation(s)
- Veronica Carnicelli
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila I-67100, Italy
| | - Anna Rita Lizzi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila I-67100, Italy
| | - Giancaterino Gualtieri
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila I-67100, Italy
| | - Argante Bozzi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila I-67100, Italy
| | - Nicola Franceschini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila I-67100, Italy
| | - Antonio Di Giulio
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila I-67100, Italy
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Maurya AK, Vinayak M. Quercetin regresses Dalton's lymphoma growth via suppression of PI3K/AKT signaling leading to upregulation of p53 and decrease in energy metabolism. Nutr Cancer 2015; 67:354-63. [PMID: 25658812 DOI: 10.1080/01635581.2015.990574] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Various oncogenes are associated with deregulation in cell proliferation, apoptosis, and cell survival, which ultimately cause cancerous growth. Phosphatidylinositol 3-kinase (PI3K) mediated signaling plays a key role in malignant transformation. Cell proliferation and cell survival of tumor cell are induced by hyper activation of PI3K, AKT1, glycolytic enzyme LDH-A, and inactivation of tumor suppressor gene p53. Dietary flavonoids such as quercetin are considered a powerful modulator of different cellular signaling pathways. The present study is focused on the role of quercetin on regulation of PI3K/AKT pathways in Dalton's lymphoma mice. Effect of quercetin was analyzed in ascite cells in terms of cell viability, glycolytic metabolism as well as expression, and level of PI3K (regulatory and catalytic subunit), AKT1, and p53 using standard methods. Results reflect hyperactivation of PI3K signaling in ascite cells of Dalton's lymphoma mice, leading to activation of AKT1 and inactivation of p53. Quercetin modulates the pathway toward suppression of lymphoma. Glycolytic metabolism was also downregulated by quercetin. Its tumor suppressor activity was confirmed by morphological parameters and longevity of mice. The findings suggest that quercetin may contribute to lymphoma prevention by downregulating PI3K-AKT1-p53 pathway as well as by glycolytic metabolism.
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Affiliation(s)
- Akhilendra Kumar Maurya
- a Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology , Banaras Hindu University , Varanasi , India
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20
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Suleria HAR, Butt MS, Anjum FM, Saeed F, Khalid N. Onion: Nature Protection Against Physiological Threats. Crit Rev Food Sci Nutr 2014; 55:50-66. [DOI: 10.1080/10408398.2011.646364] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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21
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Brisdelli F, Bennato F, Bozzi A, Cinque B, Mancini F, Iorio R. ELF-MF attenuates quercetin-induced apoptosis in K562 cells through modulating the expression of Bcl-2 family proteins. Mol Cell Biochem 2014; 397:33-43. [DOI: 10.1007/s11010-014-2169-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 07/24/2014] [Indexed: 11/24/2022]
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22
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Abstract
Food-derived flavonoid quercetin, widely distributed in onions, apples, and tea, is able to inhibit growth of various cancer cells indicating that this compound can be considered as a good candidate for anticancer therapy. Although the exact mechanism of this action is not thoroughly understood, behaving as antioxidant and/or prooxidant as well as modulating different intracellular signalling cascades may all play a certain role. Such inhibitory activity of quercetin has been shown to depend first of all on cell lines and cancer types; however, no comprehensive site-specific analysis of this effect has been published. In this review article, cytotoxicity constants of quercetin measured in various human malignant cell lines of different origin were compiled from literature and a clear cancer selective action was demonstrated. The most sensitive malignant sites for quercetin revealed to be cancers of blood, brain, lung, uterine, and salivary gland as well as melanoma whereas cytotoxic activity was higher in more aggressive cells compared to the slowly growing cells showing that the most harmful cells for the organism are probably targeted. More research is needed to overcome the issues of poor water solubility and relatively low bioavailability of quercetin as the major obstacles limiting its clinical use.
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Sassi N, Biasutto L, Mattarei A, Carraro M, Giorgio V, Citta A, Bernardi P, Garbisa S, Szabò I, Paradisi C, Zoratti M. Cytotoxicity of a mitochondriotropic quercetin derivative: Mechanisms. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS 2012; 1817:1095-106. [DOI: 10.1016/j.bbabio.2012.03.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2011] [Revised: 02/15/2012] [Accepted: 03/05/2012] [Indexed: 10/28/2022]
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24
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Brisdelli F, Perilli M, Sellitri D, Piovano M, Garbarino JA, Nicoletti M, Bozzi A, Amicosante G, Celenza G. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother Res 2012; 27:431-7. [PMID: 22628260 DOI: 10.1002/ptr.4739] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2011] [Revised: 04/17/2012] [Accepted: 04/22/2012] [Indexed: 11/12/2022]
Abstract
The purpose of this study was to investigate the effects of six lichen metabolites (diffractaic acid, lobaric acid, usnic acid, vicanicin, variolaric acid, protolichesterinic acid) on proliferation, viability and reactive oxygen species (ROS) level towards three human cancer cell lines, MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and HCT-116 (colon carcinoma). Cells were treated with different concentrations (2.5-100 μM) of these compounds for 48 h. In this comparative study, our lichen metabolites showed various cytotoxic effects in a concentration-dependent manner, and usnic acid was the most potent cytotoxic agent, while variolaric acid did not inhibit the proliferation of any of the three cell lines used. All tested lichen compounds did not exhibit free radical scavenging activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The lichen metabolites did not significantly increase the intracellular ROS level and did not prevent oxidative injury induced by t-butylhydroperoxide in HeLa cells. To better clarify the mechanism(s) of cytotoxic effect induced by protolichesterinic acid in HeLa cells, we investigated apoptotic markers such as condensation and fragmentation of nuclear chromatin and activation of caspase-3, 8 and 9. Our results revealed that the antiproliferative activity of 40 μM protolichesterinic acid in HeLa cells is related to its ability to induce programmed cell death involving caspase-3, 8 and 9 activation.
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Affiliation(s)
- Fabrizia Brisdelli
- Department of Biomedical Sciences and Technologies, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L' Aquila, Italy.
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25
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Ravi A, Mallika A, Sama V, Begum AS, Khan RS, Reddy BM. Antiproliferative activity and standardization of Tecomella undulata bark extract on K562 cells. JOURNAL OF ETHNOPHARMACOLOGY 2011; 137:1353-1359. [PMID: 21843623 DOI: 10.1016/j.jep.2011.07.067] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2010] [Revised: 07/10/2011] [Accepted: 07/30/2011] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The bark of Tecomella undulata is primarily used in the treatment of syphilis, painful swellings and cancer by traditional healers. Also, it is claimed to be useful in treating urinary discharges, enlargement of spleen, leucorrhoea, leukoderma, tumors, liver disorders, gonorrhea, gout and promotes wound healing in Indian traditional system of medicine. AIM To establish a scientific validation for the antitumor effects of Tecomella undulata bark and explore the mechanistic pathway in chronic myeloid leukemia cell line, K562. The study was further extended to standardize the extract using quercetin as biomarker. METHODS Induction of apoptosis by chloroform extract of Tecomella undulata bark (CTUB) was determined by MTT, Annexin V and caspase activation assays. The cell cycle analysis was done by flow cytometer and nuclear staining by DAPI. The standardization of the extract was performed through reverse phase-HPLC method under PDA detection. RESULT Results clearly showed the induction of apoptosis by CTUB in K562 cells. The effect was found to be dose dependent, having IC(50) of 30 μg/ml with activation of FAS, FADD, caspase 8, caspase 3/7 and fragmentation of DNA. The bioactive CTUB was determined to possess 0.03% (w/w) of quercetin. CONCLUSION The investigation clearly demonstrated the potential antitumor effect of CTUB, thereby validating the traditional claim. Quercetin, known to have anticancer activity is being reported and quantified for the first time from the bark of Tecomella undulata.
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MESH Headings
- Antineoplastic Agents, Phytogenic/analysis
- Antineoplastic Agents, Phytogenic/isolation & purification
- Antineoplastic Agents, Phytogenic/pharmacology
- Antineoplastic Agents, Phytogenic/standards
- Apoptosis/drug effects
- Bignoniaceae/chemistry
- Caspase 3/metabolism
- Caspase 7/metabolism
- Caspase 8/metabolism
- Cell Cycle/drug effects
- Cell Proliferation/drug effects
- Chromatography, High Pressure Liquid
- Chromatography, Reverse-Phase
- Dose-Response Relationship, Drug
- Fas-Associated Death Domain Protein/metabolism
- Flow Cytometry
- Hep G2 Cells
- Humans
- Inhibitory Concentration 50
- K562 Cells
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
- Plant Bark
- Plant Extracts/analysis
- Plant Extracts/isolation & purification
- Plant Extracts/pharmacology
- Plant Extracts/standards
- Plants, Medicinal
- Quercetin/analysis
- fas Receptor/metabolism
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Affiliation(s)
- Alvala Ravi
- G Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad 500 028, AP, India.
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26
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Payton F, Bose R, Alworth WL, Kumar AP, Ghosh R. 4-Methylcatechol-induced oxidative stress induces intrinsic apoptotic pathway in metastatic melanoma cells. Biochem Pharmacol 2011; 81:1211-8. [PMID: 21419106 DOI: 10.1016/j.bcp.2011.03.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2011] [Revised: 03/07/2011] [Accepted: 03/08/2011] [Indexed: 10/18/2022]
Abstract
There has been a steady rise in fatalities associated with thick melanomas (>4mm). Although understanding of the biology of the disease has improved, effective treatment strategies for patients with advanced metastatic melanoma remain elusive. Therefore, more intensive testing of agents with therapeutic potential are needed to improve survival of patients with metastatic malignant melanoma. We have tested the ability of 4-methylcatechol, a metabolite of quercetin; a naturally occurring compound that is commonly found in a variety of fruits for its potential as an anti-melanoma agent. Our results show that 4-methylcatechol inhibits proliferation of melanoma cells in culture while not affecting the growth of normal human epidermal melanocytes. Further, the ability of metastatic melanoma cells to form colonies on soft agar was also inhibited. 4-Methylcatechol caused the accumulation of cells in G2/M phase of the cell cycle and induced apoptosis. There was an increase in reactive oxygen species following treatment with 4-methylcatechol that led to apoptosis through the intrinsic mitochondrial pathway. Treatment also inhibited cell survival mediated by Akt, a key player in melanoma cell survival. Taken together our results suggest that 4-methylcatechol exhibits cytotoxicity towards metastatic malignant melanoma cells while sparing normal melanocytes and should be tested further as a potential drug candidate for malignant melanoma.
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27
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Wu LC, Lu IW, Chung CF, Wu HY, Liu YT. Antiproliferative mechanisms of quercetin in rat activated hepatic stellate cells. Food Funct 2011; 2:204-12. [DOI: 10.1039/c0fo00158a] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Tan J, Wang B, Zhu L. Regulation of survivin and Bcl-2 in HepG2 cell apoptosis induced by quercetin. Chem Biodivers 2009; 6:1101-10. [PMID: 19623560 DOI: 10.1002/cbdv.200800141] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Quercetin, a widely distributed bioflavonoid, has been shown to induce growth inhibition in a variety of human cancer cells. However, the regulation of survivin and Bcl-2 on the quercetin-induced cell-growth inhibition and apoptosis in cancer cells remains unclear. In the present study, we report that quercetin can inhibit proliferation and induce apoptosis in HepG2 cells in dose- and time-dependent manner. Hoechst 33258 and acridine orange/ethidium bromide (AO/EB) staining showed that HepG2 cells underwent the typical morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin condensation, or fragmentation after exposure to quercetin. Cell-cycle analysis reveals a significant increase of the proportion of cells in G(0)/G(1) phase. We also demonstrate that the levels of survivin and Bcl-2 protein expression in HepG2 cells decreased concurrently, and the levels of p53 protein increased significantly after treatment with quercetin by immunocytochemistry analysis. Relative activity of caspase-3 and caspase-9 increased significantly. These data clearly indicate that quercetin-induced apoptosis is associated with caspase activation, and the levels of survivin and Bcl-2. Our results indicate that the expression of survivin may be associated with Bcl-2 expression, and the inhibition expression of survivin, in conjunction with Bcl-2, might cause more pronounced apoptotic effects. Together, concurrent down-regulated survivin and Bcl-2 play an important role in HepG2 cell apoptosis induced by quercetin.
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Affiliation(s)
- Jun Tan
- Bioengineering College, Chongqing University, Chongqing, P. R. China.
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RAMADAN MOHAMEDFAWZY, SELIM ASKER MOHSENMOHAMED. ANTIMICROBICAL AND ANTIVIRIAL IMPACT OF NOVEL QUERCETIN-ENRICHED LECITHIN. J Food Biochem 2009. [DOI: 10.1111/j.1745-4514.2009.00237.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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30
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Giorgioni G, Ruggieri S, Di Stefano A, Sozio P, Cinque B, Di Marzio L, Santoni G, Claudi F. Glycosyl and polyalcoholic prodrugs of lonidamine. Bioorg Med Chem Lett 2008; 18:2445-50. [PMID: 18321702 DOI: 10.1016/j.bmcl.2008.02.046] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2008] [Revised: 02/15/2008] [Accepted: 02/17/2008] [Indexed: 10/22/2022]
Abstract
Polyhydric alcohol derivatives of the anticancer agent lonidamine (LND) have been synthesized. The increased water solubility showed by prodrugs 4, 7, and 25 together with their logP values (2.19, 2.55, and 2.54, respectively) and chemical stability might be beneficial for prodrugs absorption after oral administration. Moreover, the new prodrugs undergo enzymatic hydrolysis in plasma and release LND demonstrating that they are promising candidates for in vivo investigations.
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Affiliation(s)
- G Giorgioni
- Dipartimento di Scienze Chimiche, Università di Camerino, Via S. Agostino 1, 62032 Camerino (MC), Italy.
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