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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: RAPID COMMUNICATIONS IN MASS SPECTROMETRY; v. 25, n. 3, p. 449-452, FEB 2011.
• Web of Science Citations: 4

Abstract

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)

• FAPESP's process: 08/57471-7 - The role of fatty acid synthase activity in apoptosis, metastasis and vasculogenesis in melanoma
• Grantee: Edgard Graner
• Support Opportunities: Research Projects - Thematic Grants