Dihydrotanshinone I Targets PGAM1 to Induce SYVN1-Mediated Ubiquitination and Suppress Glycolysis in Hepatocellular Carcinoma.

ABSTRACT: Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme frequently overexpressed in hepatocellular carcinoma (HCC), contributing to tumor progression through aberrant glycolysis. Dihydrotanshinone I (DHT), a bioactive natural compound derived from Salvia miltiorrhiza , has been proposed as a potential therapeutic agent for HCC. This study aims to characterize DHT as a PGAM1-targeting agent and investigate its anti-HCC effects. We assessed the effects of DHT on PGAM1 regulation and glycolytic activity in vitro and in vivo. Using proteasomal degradation assays, we evaluated the role of Synoviolin 1 (SYVN1), an E3 ubiquitin ligase, in mediating the ubiquitination and degradation of PGAM1. The impact of DHT on key glycolytic enzymes, glucose consumption, lactate production, and ATP levels was

SUBMITTER: Xu R 

PROVIDER: S-EPMC12337087 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature