Induction of apoptosis by tea polyphenols mediated through mitochondrial cell death pathway in mouse skin tumors

Abstract

Many naturally occurring phytochemicals have shown cancer chemopreventive potential in a variety of bioassay systems. One such naturally occurring biologically active compound is tea (Camellia sinensis), which is the most consumed beverage in the world after water. The most abundant and active constituents of tea are polyphenols (epigallocatechin gallate and theaflavins). In the present study, cancer chemopreventive properties of both black tea polyphenols (BTP) and green tea polyphenols (GTP) on 7,12-dimethylbenz[a] anthracene (DMBA) induced mouse skin carcinogenesis were studied. BTP and GTP treatment showed delay in onset of tumorigenesis, reduction in cumulative number of tumors and increased tumor free survival. Both BTP and GTP were found to modulate the expression of proteins involved in apoptotic pathway. Tea polyphenols treatment along with DMBA exposure resulted in upregulation of p53, and proapoptotic protein Bax, whereas enhanced expression of antiapoptotic proteins, Bcl-2 and survivin by DMBA were downregulated. Further, we showed that tea polyphenols supplementation resulted in release of cytochrome c, caspases activation, and increase in apoptotic protease activating factor and poly (ADP-ribose) polymerase cleavage as mechanism of apoptosis induction. The results also provide strong evidence that BTP is a better chemopreventive agent against skin tumorigenesis as compared to GTP at the tested dose levels. Thus, we can conclude that the polyphenolic constituents present in black tea and green tea induce mitochondrial pathway of apoptosis and hence can be used as a potential chemopreventive agents against skin cancer. ©2009 Landes Bioscience.