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% (IC50) value (i.e. 10 μM), reduced the expression of hexokinase type-II, induced cell-cycle arrest at G1-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.

Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells

Adinolfi, Barbara
Primo
;
CARPI, SARA
Secondo
;
DA POZZO, ELEONORA;CASTAGNA, MAURA;COSTA, BARBARA;MARTINI, CLAUDIA;BRESCHI, MARIA CRISTINA;NIERI, PAOLA
Penultimo
;
FOGLI, STEFANO
Ultimo
2015

Abstract

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% (IC50) value (i.e. 10 μM), reduced the expression of hexokinase type-II, induced cell-cycle arrest at G1-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.
Adinolfi, Barbara; Carpi, Sara; Romanini, Antonella; DA POZZO, Eleonora; Castagna, Maura; Costa, Barbara; Martini, Claudia; Olesen, Søren Peter; Schmitt, Nicole; Breschi, MARIA CRISTINA; Nieri, Paola; Fogli, Stefano
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/750325
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