Plumbagin Triggers Cuproptosis in Hepatocellular Carcinoma (HCC) via the DNA-Methyltransferase 1 (DNMT1)/microRNA-302a-3p (miR-302a-3p)/ATPase Copper Transporting Beta (ATP7B) Axis.

ABSTRACT: Induction of cuproptosis in tumor cells is an emerging direction for cancer drug development. Plumbagin (PLB), a natural biological molecule, has anticancer activities, partially via copper-dependent mechanisms. But it remains unclear if PLB can induce cuproptosis in hepatocellular carcinoma (HCC). In this study, PLB showed HCC-suppressive activities and caused representative molecular phenotypes of cuproptosis, whereas tetrathiomolybdate, an inhibitor of cuproptosis, could alleviate these effects the most. The mRNA and protein expression levels of the primary hepatic copper exporter, ATPase copper transporting beta (ATP7B), decreased in PLB-treated HCC cells, which might cause the accumulation of intracellular copper and trigger cuproptosis. An upstream ATP7B-regulatory microRNA, microRNA

SUBMITTER: Wang C 

PROVIDER: S-EPMC12318818 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature