To develop innovative strategies for cancer therapy, it is necessary to identify molecular targets in the apoptotic pathway that are differentially regulated in normal and cancer cells.Many cellular factors involved in apoptosis have been identified and their roles in the apoptotic pathway are elucidated.Apoptosis is initiated through an extrinsic pathway by the interaction of cell death receptors with their ligands or an intrinsic pathway triggered by leakage of cytochromecfrom mitochondria.These result in activation of a cascade of caspase proteolysis reaction. Caspases can be divided into two groups based on the length of their prodomain and substrate specificity.The costs of publication of this article were defrayed in part by the payment of page charges.Downstream caspases such as caspase, caspase, and caspase are executioner caspases that remain dormant until the initiator caspases activate them by proteolysis. The activated executioner caspases cleave a number of structural and regulatory proteins, leading to apoptotic cell death. XIAP is the most potent caspase inhibitor in the IAP family.It has been shown that XIAP prevents the proteolytic processing of procaspase, procaspase, and procaspase by binding and blocking the activity of caspase through its BIR domain.XIAP additionally inhibits the activity of active caspase through a short linker region that precedes BIR. At present, it is still controversial whether survivin directly binds and inhibits caspase.XIAP is detected at a low level in normal adult tissues.Survivin is expressed during fetal development but not in most adult tissues. A recent study showed upregulation of survivin in of pancreatic duct cell adenocarcinoma, and survivin was expressed in early stages of neoplastic transition in pancreatic cancer cells.On the other hand, survivin was not detected in normal pancreatic tissues. Approximately of breast cancers were positive for survivin expression while surrounding normal tissues are negative.An increase in the level of survivin contributed to a higher apoptotic threshold and Revefenacin survival of the breast cancer cells. Survivin was also detected in of human colorectal cancers.Fiveyear survival rate in the stage II patients with positive survivin were significantly lower than that of the survivinnegative patients. Furthermore, a high level of XIAP was also detected in human tumors and has been shown to confer the resistance to chemotherapy drugs. A logical strategy to overcome resistance to apoptosis is to directly target the apoptotic pathway.Another promising approach is to decrease the apoptotic threshold in tumor cells by counteracting IAP function.A XAF, which is present in many normal tissues but is low or absent in tumors, abolishes the function of XIAP through direct interaction of the proteins. TARGETING INHIBITOR OF APOPTOSIS PROTEINS tion and induced apoptosis in vitro, as well as in animal tumor models at position. Interestingly, expression of survivin TA selectively induced apoptotic cell death in tumor cells but not in normal cells. Although induction of apoptotic cell death by expression of either XAF or dominantnegative survivin has been demonstrated in human tumor cells, mechanisms for selective induction in tumor cells are largely unknown.In this study, we compared the levels and activities of apoptotic effectors and inhibitors in human cancer cell lines and tissues with normal cell lines and tissues.

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