Abstract
Disulfiram (DSF), which is used to treat alcohol dependence, has been reported to have anticancer effects in various malignant tumors. We studied the anti-cancer effects and mechanism of action of DSF on cervical cancer cell lines HeLa and SiHa. The anti-cancer effects of DSF were confirmed in vivo using a xenograft tumor model. The anti-cancer effects of DSF in human head and neck squamous cell carcinoma were found to be copper (Cu)-dependent. The anti-tumor effects of DSF/Cu were time- and dose-dependent and were mediated by both autophagy and apoptosis. DSF/Cu shows stronger cytotoxicity to adenocarcinoma cell lines with higher malignant behavior, and valosin-containing protein (VCP) is its potential target. The cytotoxic effect of DSF/Cu against cervical cancer cell lines in vitro was mediated by apoptosis and autophagy simultaneously. Analysis of the clinical relevance of DSF/Cu on a xenograft animal model showed that DSF markedly stimulated tumor necrosis. DSF may contribute to improved survival of patients with cervical cancer. The antitumor characteristic of DSF can be used in the development of a new drug for advanced and refractory patients with cervical cancer.
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