Caspase-9 as a therapeutic target for treating cancer

Abstract

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

Acknowledgements

SK Srivastava is currently an International Scholar at Kyunghee University, Seoul, South Korea.

Declaration of interest

SK Srivastava was supported by in part by R01 grant CA129038 awarded by National Cancer Institute, NIH, and MRC grant2007–0054931 to Kim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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