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 up-regulation of p53, and proapoptotic protein Bax, whereas

enhanced expression of antiapoptotic proteins, Bcl-2 and survivin by DMBA were

down-regulated. 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.

This article is referred to by:

Prevention of skin cancer by green tea: Past, present and future