Introduction: Caspase-9 is the apoptotic initiator protease of the intrinsic or mitochondrial apoptotic pathway, which is activated at multi-protein activation platforms. Its activation is believed to involve homo-dimerization of the monomeric zymogens. It binds to the apoptosome to retain substantial catalytic activity. Variety of apoptotic stimuli can regulate caspase-9. However, the mechanism of action of various regulators of caspase-9 has not been summarized and compared yet. In this article, we elucidate the regulators of caspase-9 including microRNAs, natural compounds that are related to caspase-9 and ongoing clinical trials with caspase-9 to better understand the caspase-9 in suppressing cancer.
Areas covered: In this study, the basic mechanism of apoptosis pathways, regulators of caspase-9 and the development of drugs to regulate caspase-9 are reviewed. Also, ongoing clinical trials for caspase-9 are discussed.
Expert opinion: Apoptosis has crucial role in cancer, brain disease, aging and heart disease to name a few. Since caspase-9 is an initiator caspase of apoptosis, it is an important therapeutic target of various diseases related to apoptosis. Therefore, a deep understanding on the roles as well as regulators of caspase-9 is required to find more effective ways to conquer apoptosis-related diseases especially cancer.
Keywords: apoptosis; apoptosis-activating factor-1; apoptosome; cancer; caspase-3; caspase-9.