The Chemopreventive Effect of Ginsenoside Compound K Is Regulated by PARP-1 Hyperactivation, Which Is Promoted by p62-Dependent SIRT6 Degradation.

ABSTRACT:

Background and aims

Ginsenoside compound K (CK), a saponin metabolite of ginseng, exerts anticancer effects; however, its molecular mechanisms of action in lung cancer remain unclear. We investigated the involvement of silent information regulator 6 (SIRT6) and poly (ADP-ribose) polymerase 1 (PARP-1) in the anticancer effects of CK in lung cancer.

Methods and results

CK induced PARP-1 activation-mediated parthanatos via sequestosome-1/p62-mediated SIRT6 degradation and inhibited the proliferation of H460 cells. Although CK reduced procaspase-8 levels, no significant apoptotic cleavage of procaspase-3 or PARP-1 was observed. Furthermore, CK upregulated p27, p21, phospho-p53, and gamma-H2AX levels. CK increased LC3-II levels in a p62-independent manner, but p62 was upregulated

SUBMITTER: Kim SH 

PROVIDER: S-EPMC11821008 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature