Title:A Prooxidant Mechanism for the Anticancer and Chemopreventive Properties of Plant Polyphenols
Volume: 13
Issue: 14
Author(s): Husain Yar Khan, Haseeb Zubair, Mohd Fahad Ullah, Aamir Ahmad and Sheikh Mumtaz Hadi
Affiliation:
Keywords:
Anticancer, cancer chemoprevention, copper, DNA breakage, polyphenols, prooxidant action, ROS
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.
