Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties.
Plant polyphenols are important components of human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing DNA degradation in the presence of transition metal ions such as copper. Using human peripheral lymphocytes and Comet assay we have previously confirmed that resveratrol-Cu(II) is indeed capable of causing DNA degradation in cells. In this paper we show that the polyphenols alone (in the absence of added copper) are also capable of causing DNA breakage in cells. 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 polyphenols generate 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.
Azmi
Asfar Sohail
AS
Department of Biochemistry, Faculty of Life Sciences, A.M.U., Aligarh 202002, UP, India.
Bhat
Showket Hussain
SH
Hanif
Sarmad
S
Hadi
S M
SM
D000970:Antineoplastic Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002614:Chelating Agents / Q000378:metabolism; D020552:Comet Assay; D003300:Copper / Q000378:metabolism*; D004249:DNA Damage; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology; D005707:Gallic Acid / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010618:Phenanthrolines / Q000378:metabolism; D010636:Phenols / Q000378:metabolism* / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D059808:Polyphenols; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D002614:Chelating Agents; D005419:Flavonoids; D010618:Phenanthrolines; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013267:Stilbenes; D017392:Thiobarbituric Acid Reactive Substances; D005707:Gallic Acid; D003300:Copper; C002701:neocuproine; D000077185:Resveratrol