Disulfiram/Copper Combination as a Potential Therapeutic Approach for Hepatocellular Carcinoma: Targeting the ATF3-Mitochondrial Cell Death Pathway.

ABSTRACT: Hepatocellular carcinoma (HCC) represents a major public health issue globally, necessitating the urgent development of new therapies. The therapeutic efficacy of disulfiram (DSF) and copper (Cu) in HCC was investigated in the present study, focusing on cytotoxicity, mitochondrial function, and apoptosis to clarify the mechanistic basis of this drug combination. Our findings revealed a significant, dose-dependent reduction in HCC cell viability with DSF/Cu treatment. Further investigation showed increased reactive oxygen species (ROS) levels, decreased adenosine triphosphate (ATP) production, and a decline in mitochondrial membrane potential (MMP). These events culminated in the activation of caspase-9 and caspase-3, key enzymes in the apoptotic pathway, leading to cell death. Mechanistica

SUBMITTER: Cao J 

PROVIDER: S-EPMC12719560 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature