Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: involvement of endogenous copper and a putative mechanism for anticancer properties.
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.
Bhat
S H
SH
Department of Biochemistry, Faculty of Life Sciences, A.M.U., Aligarh 202002 (U.P.), India.
Azmi
A S
AS
Hadi
S M
SM
D000970:Antineoplastic Agents / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D020552:Comet Assay; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D003373:Coumaric Acids / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D053960:DNA Breaks; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016166:Free Radical Scavengers / Q000494:pharmacology; D005707:Gallic Acid / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010618:Phenanthrolines / Q000378:metabolism / Q000494:pharmacology; D011422:Propionates; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D002109:Caffeic Acids; D002614:Chelating Agents; D003373:Coumaric Acids; D004338:Drug Combinations; D016166:Free Radical Scavengers; D010618:Phenanthrolines; D011422:Propionates; D017392:Thiobarbituric Acid Reactive Substances; D005707:Gallic Acid; D003300:Copper; C002701:neocuproine; D004247:DNA; C495469:p-coumaric acid; C040048:caffeic acid