Visualizing inhibition of fatty acid synthase through mass spectrometric analysis of mitochondria from melanoma cells

Autor(es)

Zecchin, Karina G. ^{[1, 2]} ; Alberici, Luciane C. ^{[1, 3]} ; Riccio, Maria Francesca ^[4] ; Eberlin, Marcos N. ^[4] ; Vercesi, Anibal E. ^[1] ; Graner, Edgard ^[2] ; Catharino, Rodrigo R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas UNICAMP, Dept Patol Clin, Fac Ciencias Med, BR-13083887 Campinas, SP - Brazil

^[2] Univ Estadual Campinas UNICAMP, Dept Diagnost Oral, Fac Odontol Piracicaba, BR-13414018 Piracicaba, SP - Brazil

^[3] Univ Sao Paulo, Dept Quim & Fis, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Estadual Campinas UNICAMP, Inst Quim, Lab ThoMSon Espectrometria Massas, BR-13083887 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: RAPID COMMUNICATIONS IN MASS SPECTROMETRY; v. 25, n. 3, p. 449-452, FEB 2011.
• Citações Web of Science: 4

Resumo

Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid palmitate. In contrast to most normal cells, FASN is overexpressed in a variety of human cancers including cutaneous melanoma, in which its levels of expression are associated with a poor prognosis and depth of invasion. Recently, we have demonstrated the mitochondrial involvement in FASN inhibition-induced apoptosis in melanoma cells. Herein we compare, via electrospray ionization mass spectrometry (ESI-MS), free fatty acids (FFA) composition of mitochondria isolated from control (EtOH-treated cells) and Orlistat-treated B16-F10 mouse melanoma cells. Principal component analysis (PCA) was applied to the ESI-MS data and found to separate the two groups of samples. Mitochondria from control cells showed predominance of six ions, that is, those of m/z 157 (Pelargonic, 9:0), 255 (Palmitic, 16:0), 281 (Oleic, 18:1), 311 (Arachidic, 20:0), 327 (Docosahexaenoic, 22:6) and 339 (Behenic, 22:0). In contrast, FASN inhibition with Orlistat changes significantly mitochondrial FFA composition by reducing synthesis of palmitic acid, and its elongation and unsaturation products, such as arachidic and behenic acids, and oleic acid, respectively. ESI-MS of mitochondria isolated from Orlistat-treated cells presented therefore three major ions of m/z 157 (Pelargonic, 9:0), 193 (unknown) and 199 (Lauric, 12:0). These findings demonstrate therefore that FASN inhibition by Orlistat induces significant changes in the FFA composition of mitochondria. Copyright (C) 2011 John Wiley \& Sons, Ltd. (AU)

• Processo FAPESP: 09/51948-9 - Identificacao de biomarcadores de risco cardiometabolico: uma abordagem metabolomica
• Beneficiário: Rodrigo Ramos Catharino
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/57471-7 - Análise da participação da produção endógena de ácidos graxos nos mecanismos de apoptose, metástase e vasculogênese em melanoma
• Beneficiário: Edgard Graner
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/54639-1 - Caracterização dos mecanismos de morte celular diante da inibição da síntese endógena de ácidos graxos em linhagem celular derivada de melanoma
• Beneficiário: Karina Gottardello Zecchin
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado