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.

• Authors: Bonglee Kim, Sanjay K Srivastava, Sung-Hoon Kim
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 19 Issue 1 Pg. 113-27 (Jan 2015) ISSN: 1744-7631 [Electronic] England
• PMID: 25256701 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Biological Products
• Caspase 9

Topics

• Animals
• Apoptosis (physiology)
• Biological Products (pharmacology)
• Caspase 9 (metabolism)
• Humans
• Neoplasms (drug therapy, metabolism)