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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 7
[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
Total Affiliations: 4
Document type: Journal article
Source: RAPID COMMUNICATIONS IN MASS SPECTROMETRY; v. 25, n. 3, p. 449-452, FEB 2011.
Web of Science Citations: 4

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 type: Research Projects - Thematic Grants