Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission.

ABSTRACT: Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells. Pharmacological induction of excessively asymmetric mitofission-associated cell death (MFAD) by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy. By screening a series of pan-inhibitors, we identified pracinostat, a pan-histone deacetylase (HDAC) inhibitor, as a novel MFAD inducer, that exhibited a significant anticancer effect on colorectal cancer (CRC) in vivo and in vitro. Pracinostat increased the expression of cyclin-dependent kinase 5 (CDK5) and induced its acetylation at residue lysine 33, accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynami

SUBMITTER: Liang XL 

PROVIDER: S-EPMC10657975 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature