Disulfiram/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS/MAPK and Ferroptosis Pathways.

ABSTRACT: Disulfiram/copper (DSF/Cu) is a promising antitumor reagent for clinical application due to its excellent anticancer activity and safety. However, the anticancer mechanism of DSF/Cu has not been fully elucidated. Our study showed that DSF/Cu strongly induced cytotoxic effects on both nasopharyngeal carcinoma (NPC) cells and α-smooth muscle actin (α-SMA)-positive fibroblasts. Fluorescence activated cell sorting (FACS) analysis further showed that DSF/Cu induced a higher late apoptosis rate in α-SMA-positive fibroblasts than in tumor cells, and DSF/Cu promoted apoptosis and necrosis by an aldehyde dehydrogenase (ALDH)-independent method. Furthermore, we found that the antitumor activity of DSF/Cu against NPC cells occurred through ROS/MAPK and p53-mediated ferroptosis pathways, and that the

SUBMITTER: Li Y 

PROVIDER: S-EPMC7017005 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature