Progress and clinical application of TRAIL-induced apoptosis in cancer / 中国药理学通报

ABSTRACT

TNF related apoptosis inducing ligand (TRAIL) is a new identified member of TNF family, which selectively kills a broad spectrum of tumor cells, but nontoxic to most normal cells. TRAIL triggers tumor cell apoptosis via death receptor DR4 and DR5 anchored in the cell surface, which is mediated through intracellular induced apoptosis proteins. The major pathway of its action proceeds through the formation of DSIC and activation of caspase8. The apoptotic processes follow two signal pathways, namely the mitochondrial independent activation of caspase3, and mitochondrial dependent apoptosis through the cleavage of BID by caspase8, the release of cytochrome C, the formation of apoptosome, and activation of caspase9 and the downstream apoptosis. In previous researches, it is shown that nontagged TRAIL proved to be noncytotoxic to hepatocytes in monkeys and chimpanzees and to human normal hepatocytes. Thus, the nontagged TRAIL has attracted great attention in recent years as a promising anti cancer reagent.