Analysis of the antitumor activity of clotrimazole on A375 human melanoma cells

Aim: The current study was designed to characterize the anticancer effects of clotrimazole on human cutaneous melanoma cells. Materials and Methods: The v-raf murine sarcoma viral oncogene homolog B1 V600E mutant melanoma cell line A375 was used as an in vitro model. Characterization tools included analyses of cell viability, gene expression, cell-cycle progression, annexin V reactivity and internucleosomal DNA fragmentation. Results: Clotrimazole induced cytotoxicity in A375 human melanoma cells without significant changes of human keratinocyte cell viability. Clotrimazole, at a concentration that approximates the inhibitory concentration 50% (IC) value (i.e. 10 ?M), reduced the expression of hexokinase type-II, induced cell-cycle arrest at G-S phase transition, altered annexin V reactivity and induced DNA fragmentation without evidence of necrosis. Conclusion: The current study provides evidence of a remarkable pro-apoptotic effect by clotrimazole against human melanoma cells, with a different mechanism of action and timeline of the apoptosis-related events when compared to cisplatin.