Antifungal Agents Induce Apoptotic and Non‐Apoptotic Cell Death in Human Melanoma Cells

Abstract

Patients with melanoma, the most aggressive form of skin cancer, have poor survival rates due to the resistance of advanced stage tumors to chemotherapy. This resistance appears to involve the dysregulation of apoptosis, such that inhibition of apoptotic progression allows melanoma cells to survive after treatment. We previously reported a potentially novel treatment for melanoma, where antifungal agents led to profound decreases in growth and proliferation of human melanoma cells. Our objective here was to analyze cell death pathways induced in human melanoma cell lines following treatment with antifungal agents. Cell death pathways were investigated via flow cytometry, cell proliferation assays, and immunoblotting after treatments.Several lines of human melanoma and normal skin cells were analyzed. Apoptosis, via flow cytometry and analysis of activated caspases and PARP1 cleavage, was observed in all melanoma lines after treatment with clotrimazole and econazole. Caspase‐independent cell death was also observed in most melanoma lines after similar treatments. No extensive cell death was induced by these treatments in noncancerous human skin cells. These results indicated that antifungal agents selectively induced cytotoxicity in human melanoma lines. Because varying levels of cell death were observed among different melanoma lines after antifungal treatment, further studies will be required to ascertain the reason for these differential responses to treatment. Taken together, these results indicated that clotrimazole and econazole initiated apoptotic and non‐apoptotic cell death in human melanoma cells.In conclusion, this study demonstrated the induction of apoptotic and non‐apoptotic cell death in human melanoma skin cell lines after treatment with antifungal agents. Differential levels of various cell death pathways were observed among all melanoma lines. This was corroborated by the various levels of efficacious treatment produced by these agents. Taken together, we conclude that clotrimazole and econazole induce cell death in human melanoma cells. These agents thus appear to have in vitro efficacy toward the treatment of human melanoma.Support or Funding InformationThis research was supported in part by the Bower, Bennet & Bennet Endowed Chair Award from the Ohio Northern University College of Pharmacy and the Ohio Northern University Summer Research stipend.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.