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Title: Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties

Abstract

Plant-derived dietary material contains several classes of polyphenols such as flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing cellular DNA degradation in the presence of transition metal ions such as copper. Earlier we have shown that the stilbene resveratrol is able to mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major constituent of coffee, is also capable of DNA breakage in human peripheral lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that caffeic acid generates oxidative stress in lymphocytes, which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action.

Authors:
 [1];  [1];  [2]
  1. Department of Biochemistry, Faculty of Life Sciences, A.M.U., Aligarh 202002 (U.P.) (India)
  2. Department of Biochemistry, Faculty of Life Sciences, A.M.U., Aligarh 202002 (U.P.) (India). E-mail: smhadi@vsnl.com
Publication Date:
OSTI Identifier:
20976858
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 218; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2006.11.022; PII: S0041-008X(06)00450-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BEVERAGES; BIOLOGICAL STRESS; CHROMATIN; CLEAVAGE; COMETS; COPPER; COPPER IONS; DNA; FLAVONOIDS; LYMPHOCYTES; OXIDATION; OXYGEN; POLYPHENOLS; STILBENE

Citation Formats

Bhat, S.H., Azmi, A.S., and Hadi, S.M.. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.11.022.
Bhat, S.H., Azmi, A.S., & Hadi, S.M.. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties. United States. doi:10.1016/j.taap.2006.11.022.
Bhat, S.H., Azmi, A.S., and Hadi, S.M.. Thu . "Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties". United States. doi:10.1016/j.taap.2006.11.022.
@article{osti_20976858,
title = {Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties},
author = {Bhat, S.H. and Azmi, A.S. and Hadi, S.M.},
abstractNote = {Plant-derived dietary material contains several classes of polyphenols such as flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing cellular DNA degradation in the presence of transition metal ions such as copper. Earlier we have shown that the stilbene resveratrol is able to mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major constituent of coffee, is also capable of DNA breakage in human peripheral lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that caffeic acid generates oxidative stress in lymphocytes, which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action.},
doi = {10.1016/j.taap.2006.11.022},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 218,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}