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

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

Physiology of circulation, kidney and lung

13 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Anticancer Research
Vol/bind	35
Udgave nummer	7
Sider (fra-til)	3781-6
Antal sider	6
ISSN	0250-7005
Status	Udgivet - 1 jul. 2015

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http://ar.iiarjournals.org/content/35/7/3781.long

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title = "Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells",

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.",

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

author = "Barbara Adinolfi and Sara Carpi and Antonella Romanini and {Da Pozzo}, Eleonora and Maura Castagna and Barbara Costa and Claudia Martini and S{\o}ren-Peter Olesen and Nicole Schmitt and Breschi, {Maria Cristina} and Paola Nieri and Stefano Fogli",

year = "2015",

month = jul,

day = "1",

language = "English",

volume = "35",

pages = "3781--6",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "7",

}

TY - JOUR

T1 - Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells

AU - Adinolfi, Barbara

AU - Carpi, Sara

AU - Romanini, Antonella

AU - Da Pozzo, Eleonora

AU - Castagna, Maura

AU - Costa, Barbara

AU - Martini, Claudia

AU - Olesen, Søren-Peter

AU - Schmitt, Nicole

AU - Breschi, Maria Cristina

AU - Nieri, Paola

AU - Fogli, Stefano

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - Annexin A5

KW - Antineoplastic Agents

KW - Apoptosis

KW - Cell Line, Tumor

KW - Cell Survival

KW - Cisplatin

KW - Clotrimazole

KW - DNA Fragmentation

KW - G1 Phase Cell Cycle Checkpoints

KW - Humans

KW - Keratinocytes

KW - Melanoma

M3 - Journal article

C2 - 26124322

SN - 0250-7005

VL - 35

SP - 3781

EP - 3786

JO - Anticancer Research

JF - Anticancer Research

IS - 7

ER -

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

Abstract

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