Inhibition of anti-apoptotic Bcl-2 family proteins by natural polyphenols: new avenues for cancer chemoprevention and chemotherapy.

Amongst the most promising chemopreventive agents, certain natural polyphenols have recently received a great deal of attention from the scientific community, nutritionists, the pharmaceutical industry and the public, due to their demonstrated inhibitory activity against tumorigenesis. In view of their anticancer properties, these compounds also hold great promise as potential chemotherapeutic agents. However, to translate these chemopreventive agents into chemotherapeutic compounds, their exact mechanism of action must be delineated. The aim of this manuscript is to review recent findings suggesting that certain natural products bind and antagonize the anti-apoptotic effects of Bcl-2 family proteins such as Bcl-x(L) and Bcl-2. We will summarize recent studies that were aimed at the identification of the molecular targets of natural polyphenols and at the characterization of their mechanism of action on a molecular level. We will emphasize the importance of these findings that resides not only in the opportunity for the development of novel cancer treatments with these compounds, but also in the structural information that can be used for the design and development of novel and more effective semi-synthetic analogues. The finding reviewed here should encourage the study of possible direct effects of other dietary compounds on Bcl-2 family proteins.