title: A prooxidant mechanism for the anticancer and chemopreventive properties of plant polyphenols.
abstract: Plant-derived polyphenols, a prominent class of phytochemicals, are considered important components of human diet. A number of them are known to possess chemopreventive and therapeutic properties against various diseases including cancer. Several studies using cancer cell lines and animal models of carcinogenesis have shown that a wide range of polyphenols possess anticancer and apoptosis-inducing properties. Notably, an important aspect of the chemopreventive action of polyphenols is their differential activity in selectively targeting cancer cells while sparing normal cells. However, the mechanism through which polyphenols modulate their cancer cell selective anticancer effects has not been clearly delineated. In this regard, identification of a definitive anticancer mechanism of polyphenols would contribute to establish them as potent lead compounds for the synthesis of novel anticancer drugs. Although polyphenols are generally recognized as antioxidants, they also act as prooxidants inducing DNA degradation in the presence of metal ions such as copper. Based on our own observations and those of others, a mechanism for the anticancer properties of polyphenols that involves mobilization of chromatin-bound copper and consequent prooxidant action leading to cell death, was proposed. Since it is known that tissue and cellular copper levels are significantly elevated in a number of malignancies, cancer cells would be more subject to redox cycling between copper ions and polyphenols to generate reactive oxygen species (ROS) responsible for DNA breakage. This review discusses such a copper-dependent prooxidant mechanism of action of polyphenols that accounts for their observed chemopreventive properties, as also for their preferential cytotoxicity towards cancer cells.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
authors.forename: Husain Yar
authors.initials: HY
authors.lastname: Khan
authors.forename: Haseeb
authors.initials: H
authors.lastname: Zubair
authors.forename: Mohd Fahad
authors.initials: MF
authors.lastname: Ullah
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.forename: Sheikh Mumtaz
authors.initials: SM
authors.lastname: Hadi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods; D003300:Copper / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D016877:Oxidants; D059808:Polyphenols; D017382:Reactive Oxygen Species; D003300:Copper