Structure of Some Green Tea Catechins and the Availability of Intracellular Copper Influence Their Ability to Cause Selective Oxidative DNA Damage in Malignant Cells.

Mohd Farhan,Mir Waqas Alam,Asim Rizvi,Sheikh Mumtaz Hadi,Mohammad Aatif,Aamir Ahmad

doi:10.3390/biomedicines10030664

Mohd Farhan, Mir Waqas Alam + Show 4 more

Open Access

https://doi.org/10.3390/biomedicines10030664

Copy DOI

Abstract

The possible roles of elevated endogenous copper levels in malignant cells are becoming increasingly understood at a greater depth. Our laboratory has previously demonstrated that tea catechins have the ability to mobilize endogenous copper and undergo a Fenton-like reaction that can selectively damage cancer cells. In this communication, by using a diverse panel of malignant cell lines, we demonstrate that the ability of the catechin family [(−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin (EC), and (+)-catechin (C)] to induce apoptosis is dependent on their structure. We further confirm that reactive oxygen species (ROS) are the terminal effectors causing copper-mediated DNA damage. Our studies demonstrate the role of cellular copper transporters CTR1 and ATP7A in the survival dynamics of malignant cells post-EGCG exposure. The results, when considered together with our previous studies, highlight the critical role that copper dynamics and mobilization plays in cancer cells and paves the way for a better understanding of catechins as nutraceutical supplements for malignancies.

Highlights

The progression of clinical malignancies is a complex phenomenon, which is regulated by a large number of factors, that can influence the promotion and progression of disease.Dietary constituents, polyphenolic compounds [1], have been shown to affect malignancies by causing selective cell death of malignant cells [2,3]
We have previously shown that the prooxidant activity plant-derived polyphelevels is demonstrated in both solid tumors as well as in bloodof malignancies nols, We by which they mediate their selective anticancer action, is a consequence of the sehave previously shown that the prooxidant activity of plant-derived polyphenols, lective elevation of copper levels in malignant cells as compared to non-malignant conby which they mediate their selective anticancer action, is a consequence of the selective trols
Our studies demonstrate that plant-derived polyphenolics react with cellular elevation of copper levels in malignant cells as compared to non-malignant controls [3,21]

Summary

Introduction

Polyphenolic compounds [1], have been shown to affect malignancies by causing selective cell death of malignant cells [2,3]. Catechins are a class of polyphenols derived primarily from tea [4], which include (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECG), (+)-gallocatechin (GC),. Experimental evidence from our lab [5,6] and those of others [7,8] has shown that EGCG is the most potent amongst this class of molecules in causing malignant cell death. There is enough literature to suggest that, in cell lines, catechins can affect a variety of metabolic and signaling pathways [9]. These molecular events may result in cancer cell growth inhibition, apoptosis, inhibition of invasion, angiogenesis, and metastasis [9,10].

Methods

Results

Conclusion