Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: A potential role in cancer chemoprevention
| Autor: | Hussain Arif, Aamir Sohail, S.M. Hadi, Aamir Ahmad, Mohd Farhan, Ahmed Abdur Rehman |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Flavonols Cations Divalent Apoptosis Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Structural Biology Cell Line Tumor Humans MTT assay Kaempferols Molecular Biology Flavonoids chemistry.chemical_classification Reactive oxygen species food and beverages Epithelial Cells General Medicine Oxidants Pro-oxidant Antineoplastic Agents Phytogenic Galangin Comet assay 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer cell Quercetin Myricetin Reactive Oxygen Species Oxidation-Reduction Copper Fisetin DNA Damage |
| Zdroj: | International Journal of Biological Macromolecules. 106:569-578 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2017.08.049 |
| Popis: | Flavonoids, a class of polyphenols are known to be effective inducers of apoptosis and cytotoxicity in cancer cells. It is believed that antioxidant activity of polyphenols cannot fully account for induction of apoptosis and chemotherapeutic prevention in various cancers. In this article, by employing single cell alkaline gel electrophoresis (comet assay), we established that antioxidants, flavonoids such as (myricetin=MN, fisetin=FN, quercetin=QN, kaempferol=KL and galangin=GN) can cause cellular DNA breakage, also act as pro-oxidant in presence of transition metal ion such as copper. It was observed that the extent of cellular DNA breakage was found significantly higher in presence of copper. Hydroxyl radicals are generated as a sign of flavonoids' pro-oxidant nature through redox recycling of copper ions. Further, a dose-dependent inhibition of proliferation of breast cancer cells MDA-MB-231 by MN was found leading to pro-oxidant cell death, as assessed by MTT assay. Since levels of copper are considerably elevated in tissue, cell and serum during various malignancies, suggesting that cancer cells would be more subject to copper induced oxidative DNA breakage. Such a copper dependent pro-oxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells. |
| Databáze: | OpenAIRE |
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