Barbara Adinolfi1, Sara Carpi2, Antonella Romanini3, Eleonora Da Pozzo2, Maura Castagna4, Barbara Costa2, Claudia Martini2, Søren-Peter Olesen5, Nicole Schmitt5, Maria Cristina Breschi2, Paola Nieri2, Stefano Fogli6. 1. Nello Carrara Institute of Applied Physics, National Research Council, Sesto Fiorentino, Florence, Italy. 2. Department of Pharmacy, University of Pisa, Pisa, Italy. 3. Medical Oncology Unit, University Hospital of Pisa, Pisa, Italy. 4. Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy. 5. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Department of Pharmacy, University of Pisa, Pisa, Italy stefano.fogli@farm.unipi.it.
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. Copyright
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 B1V600E 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 humanmelanoma 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 humanmelanoma cells, with a different mechanism of action and timeline of the apoptosis-related events when compared to cisplatin. Copyright
Authors: Andrew J McDonald; Katherine M Curt; Ruchi P Patel; Hanna Kozlowski; Dan L Sackett; Robert W Robey; Michael M Gottesman; Susan E Bates Journal: Exp Cell Res Date: 2018-12-21 Impact factor: 3.905