A Prooxidant Mechanism of Cancer Chemopreventive Properties of Plant Polyphenols

INTRODUCTIONS: In the last couple of decades there has been some interest in alternative mechanisms of apoptosis induction which do not involve caspases. This is particularly of interest in relation to cancer cells. We have hypothesized that mobilization of endogenous copper ions by plant polyphenol...

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Published in:Indian journal of clinical biochemistry 2022-05, Vol.32 (S1), p.S33
Main Authors: Hadi, S.M, Farhan, Mohd
Format: Article
Language:English
Subjects:
Analysis
Apoptosis
Cancer
Care and treatment
Catechin
Green tea
Prevention
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Summary:INTRODUCTIONS: In the last couple of decades there has been some interest in alternative mechanisms of apoptosis induction which do not involve caspases. This is particularly of interest in relation to cancer cells. We have hypothesized that mobilization of endogenous copper ions by plant polyphenols such as EGCG and consequent oxidative degradation of cellular DNA could be an important mechanism of their anticancer properties. OBJECTIVES :Over the years we have validated our hypothesis to a considerable degree. We further confirm the hypothesis by using analogues of EGCG to identify the structural features of tea catechins important for mobilizing endogenous copper and breakage of cellular DNA in cancer cells. METHODOLOGY: Comet assay to study DNA breakage, MTT assay for cell proliferation and Histone/ DNA Elisa for apoptosis induction was used to examine the catechin mediated oxidative breakage of cellular DNA in various cancer cell lines. RESULTS & CONCLUSION: Catechins have been shown to inhibit cell proliferation and induce apoptosis in different cancer cell lines and that such cell death is prevented to a significant extent by copper chelator neocuproine. Further, normal breast epithelial cells (MCF-10A), cultured in a medium supplemented with copper (MCF-10A-Cu), become sensitized to EGCG induced growth inhibition. Copper transporters Ctr1 and ATP7A are found to have an increased expression in MCF-10A-Cu cells and EGCG inhibits the expression of both the copper transporters in such cells. Moreover, silencing of copper transporter Ctr1 by siRNA reduces the sensitivity of MCF-10A-Cu cells to EGCG. We conclude that the position and the number of hydroxyl groups in various catechins determine their capacity to mobilize endogenous copper and degrade cellular DNA. KEYWORDS: Green tea catechins, Cancer cells, Hydroxyl groups
ISSN:0970-1915