Anti-apoptotic proteins-targets for chemosensitization of tumor cells and cancer treatment

Apoptosis or programmed cell death is an essential process not only for the normal development and function of multi-cellular organisms but it is also an important phenomenon in tumor cells killing. Numerous studies have indicated that non surgical cancer therapies eliminate tumor cells by activating apoptosis. The central regulators of apoptosis are proteins of the Bcl-2 family. In a wide variety of human tumors, the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-(XL)) was found. Moreover, it was revealed that high levels of these proteins block the action of many chemotherapeutic drugs. Due to this fact the inhibition of anti-apoptotic function of Bcl-2 proteins could be a strategy for either to restore the normal apoptotic process in tumor cells or to make them susceptible for chemo- and radio-therapeutic treatment. Three alternative therapeutic strategies for the repression of cytoprotective activity of anti-apoptotic proteins in tumor cells are reviewed in this article.