Ponicidin Promotes Hepatocellular Carcinoma Mitochondrial Apoptosis by Stabilizing Keap1-PGAM5 Complex.

ABSTRACT: Ponicidin is a diterpenoid with demonstrated antitumor activity in clinical trials. However, the specific function and mechanism of action against hepatocellular carcinoma (HCC) remain unknown. In this study, it is found that ponicidin significantly inhibited the proliferation and migration of HCC cells. It is shown that ponicidin targets Keap1 and promotes the formation of the Keap1-PGAM5 complex, leading to the ubiquitination of PGAM5, using biotin-labeled ponicidin for target fishing and the HuProt^TM Human Proteome Microarray V4.0. Ponicidin is found to activate the cysteine-dependent mitochondrial pathway via PGAM5, resulting in mitochondrial damage and ROS production, thereby promoting mitochondrial apoptosis in HepG2 cells. The first in vitro cocrystal structure of the PGA

SUBMITTER: Zhao B 

PROVIDER: S-EPMC11481384 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature