Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions.
We previously reported a synergistic anticancer action of clioquinol and docosahexaenoic acid (DHA) in human cancer cells. However, clioquinol has been banned from the clinic due to its neurotoxicity. This study identified disulfiram (DSF) as a substitute compound to clioquinol, acting in concert with DHA to more effectively kill cancer cells and suppress tumor growth. Treatment with DSF and DHA induced greater apoptotic cell death and suppression of tumor growth in vitro and in vivo, as compared to DSF and DHA used alone. Mechanistic studies demonstrated that DSF enhances DHA-induced cellular oxidative stress as evidenced by up-regulation of Nrf2-mediated heme oxygenase 1 (HO-1) gene transcription. On the other hand, DHA was found to enhance DSF-induced suppression of mammosphere formation and stem cell frequency in a selected cancer model system, indicating that alterations to cancer cell stemness are involved in the combinatory anticancer action of DSF and DHA. Thus, DHA and DSF, both clinically approved drugs, act in concert to more effectively kill cancer cells. This combinatory action involves an enhancement of cellular oxidative stress and suppression of cancer cell stemness.
['Jiao|Yang|Y|', 'Hannafon|Bethany N|BN|', 'Zhang|Roy R|RR|', 'Fung|Kar-Ming|KM|', 'Ding|Wei-Qun|WQ|']
D000970:Antineoplastic Agents D017209:Apoptosis D001943:Breast Neoplasms D049109:Cell Proliferation D002470:Cell Survival D004221:Disulfiram D004281:Docosahexaenoic Acids D004357:Drug Synergism D005260:Female D051547:Heme Oxygenase-1 D006801:Humans D014411:Neoplastic Stem Cells D010051:Ovarian Neoplasms D018384:Oxidative Stress D018874:Spheroids, Cellular D014407:Tumor Cells, Cultured
docosahexaenoic acid disulfiram oxidative stress cancer stem cell nuclear factor (erythroid-derived 2)-like 2