Ursolic acid inhibited growth of hepatocellular carcinoma HepG2 cells through AMPKα-mediated reduction of DNA methyltransferase 1

摘要: Hepatocellular carcinoma (HCC), the major histological subtype of primary liver cancer, remains one most common malignancies worldwide. Due to complicated pathogenesis this malignancy, outcome for comprehensive treatment is limited. Chinese herbal medicine (CHM) emerging as a promising choice its multi-targets and coordinated intervention effects against HCC. Ursolic acid (UA), natural pentacyclic triterpenoid carboxylic found in CHM, exerts anti-tumor an effective compound cancer prevention therapy. However, molecular mechanisms underlying action UA remain largely unknown. In study, we showed that inhibited growth HCC cells induced apoptosis dose- time-dependent fashion. Furthermore, phosphorylation AMP-activated protein kinase alpha (AMPKα) suppressed expression DNA methyltransferase 1 (DNMT1) dose-dependent manner. The inhibitor AMPK, C blocked, while activator metformin augmented effect on DNMT1 expression. addition, transcription factor Sp1. Conversely, overexpression Sp1 reversed cell growth. Collectively, our results show first time inhibits through AMPKα-mediated inhibition Sp1; turn DNMT1. This study reveals potential novel mechanism by which controls suggests could be target chemoprevention treatment.