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

Barbara Adinolfi, Sara Carpi, Antonella Romanini, Eleonora Da Pozzo, Maura Castagna, Barbara Costa, Claudia Martini, Søren-Peter Olesen, Nicole Schmitt, Maria Cristina Breschi, Paola Nieri, Stefano Fogli

13 Citations (Scopus)

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.

Original languageEnglish
JournalAnticancer Research
Volume35
Issue number7
Pages (from-to)3781-6
Number of pages6
ISSN0250-7005
Publication statusPublished - 1 Jul 2015

Keywords

  • Annexin A5
  • Antineoplastic Agents
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • Cisplatin
  • Clotrimazole
  • DNA Fragmentation
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Keratinocytes
  • Melanoma

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