Please use this identifier to cite or link to this item: https://ninho.inca.gov.br/jspui/handle/123456789/9244
Title: Phosphatidylinositol-3-kinase as a putative target for anticancer action of clotrimazole
Authors: Furtado, Cristiane Marques
Marcondes, Mariah Celestino
Carvalho, Renato Sampaio
Penna, Mauro Sola
Zancan, Patrícia
Keywords: Antineoplásicos
Antineoplastic Agents
Metabolismo
Metabolism
Autofagia
Autophagy
Apoptose
Apoptosis
Issue Date: 2015
Publisher: The International Journal of Biochemistry & Cell Biology
Citation: FURTADO, Cristiane Marques et al. Phosphatidylinositol-3-kinase as a putative target for anticancer action of clotrimazole. The International Journal of Biochemistry & Cell Biology, v. 62, p. 132–141, 2015.
Abstract: Clotrimazole (CTZ) has been proposed as an antitumoral agent because of its properties that inhibit gly colytic enzymes anddetachthemfromthe cytoskeleton.However,thebroadeffects ofthedrug, e.g., acting on different enzymes and pathways, indicate that CTZ might also affect several signaling pathways. In this study, we show that CTZ interferes with the human breast cancer cell line MCF-7 after a short incubation period (4 h), thereby diminishing cell viability, promoting apoptosis, depolarizing mitochondria, inhibi ting key glycolytic regulatory enzymes, decreasing the intracellular ATP content, and permeating plasma membranes. CTZ treatment also interferes with autophagy. Moreover, when the incubation is performed under hypoxic conditions, certain effects of CTZ are enhanced, such as phosphatidylinositol-3-phosphate kinase (PI3K), which is inhibited upon CTZ treatment; this inhibition is potentiated under hypoxia. CTZ induced PI3K inhibition is not caused by upstream effects of CTZ because the drug does not affect the interaction of the PI3K regulatory subunit and the insulin receptor substrate (IRS)-1. Additionally, CTZ directly inhibits human purified PI3K in a dose-dependent and reversible manner. Pharmacologic and in silico results suggest that CTZ may bind to the PI3K catalytic site. Therefore, we conclude that PI3K is a novel, putative target for the antitumoral effects of CTZ, interfering with autophagy, apoptosis, cell division and viability.
Description: p. 132–141,: il. p&b.
URI: http://sr-vmlxaph03:8080/jspui/handle/123456789/9244
ISSN: 1357-2725
Appears in Collections:Artigos de Periódicos da área de Farmácia



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