APOPTOSIS IN CANCER THERAPY

Apoptosis is a physiological cell suicide program that is critical for the development and maintenance of healthy tissues. Therefore, aberration of this process can be detrimental. Many types of cancer are characterized by a dysregulated apoptotic pathway, including down-regulated death receptor pathway function and abnormal Bcl-2 pathway function. The major problem in cancer treatment is the development of cells resistant to drugs and antiapoptotic machinery. Therefore, apoptosis induction can be the most potent defense against cancer. The relation between carcinogenesis and dysregulation of apoptosis is well known; therefore, any therapeutic strategy that specifically triggers apoptosis in cancer cells might have potential therapeutic value. One possibility is to use biological active compounds (naturally occurring antioxidant compounds) to eliminate premalignant/malignant cells by inducing them to undergo apoptosis. Death receptors belonging to the tumor necrosis factor (TNF) receptor gene superfamily (Fas/CD95/APO-1, TRAIL/APO-2L) play a central role in apoptosis because, by activating them, we can finally cause the cell's apoptotic demise. TRAIL (TNF-related apoptosis-inducing ligand) is a death receptor able to induce apoptosis in a wide range of transformed cell lines but not in normal cells. We use biologically active agents such as polyphenols (e.g., resveratrol, vineatrol) to increase tumor cells' sensitivity to apoptosis. Our study presents the results regarding B-cell chronic lymphocytic leukemia, a neoplastic disorder characterized by defective apoptosis. The tumoral cells do not frequently express Fas receptors, so they are resistant to its apoptotic action. They also present up-regulated expression of some antiapoptotic proteins (i.e., iNOS and Bcl-2). We try to modulate apoptosis with biologically active compounds.