Mechanistic Insights into the Anti-Hepatocellular Carcinoma Effects of ACY-1215: p53 Acetylation and Ubiquitination Regulation.

ABSTRACT: As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, a selective Histone deacetylase 6 (HDAC6) inhibitor, and its mechanism targeting p53 regulation. In vitro studies conducted with HepG2 and SMMC-7721 cells revealed that ACY-1215 markedly inhibited HCC cell proliferation, migratory capacity, and invasive potential, as evidenced by CCK-8, colony formation, and Transwell assays. Furthermore, ACY-1215 induced caspase-dependent apoptosis. Mechanistically, ACY-1215 enhanced p53 acetylation by disrupting HDAC6-p53 interaction, thereby stabilizing p53 protein levels. Concurrently, it inhibited Murine Double Minute 2 (MDM2)-mediated ubiquitination, blocking prote

SUBMITTER: Yin Y 

PROVIDER: S-EPMC12110493 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature