Artículos de revistas
Visualizing Inhibition Of Fatty Acid Synthase Through Mass Spectrometric Analysis Of Mitochondria From Melanoma Cells
Registro en:
Rapid Communications In Mass Spectrometry. , v. 25, n. 3, p. 449 - 452, 2011.
9514198
10.1002/rcm.4875
2-s2.0-78651290740
Autor
Zecchin K.G.
Alberici L.C.
Riccio M.F.
Eberlin M.N.
Vercesi A.E.
Graner E.
Catharino R.R.
Institución
Resumen
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. © 2011 John Wiley & Sons, Ltd. 25 3 449 452 Smith, S., (1994) FASEB J, 8, p. 1248 Menendez, J.A., Lupu, R., (2007) Nat. Rev. Cancer, 7, p. 763 Weiss, L., Hoffmann, G.E., Schreiber, R., (1986) Biol. Chem. Hoppe Seyler, 367, p. 905 Kuhajda, F.P., (2000) Nutrition, 16, p. 202 Alo, P.L., Visca, P., Framarino, M.L., (2000) Oncol. Rep., 7, p. 1383 Pizer, E.S., Jackisch, C., Wood, F.D., (1996) Cancer Res., 56, p. 2745 Pizer, E.S., Wood, F.D., Heine, H.S., (1996) Cancer Res., 56, p. 1189 Gansler, T.S., Hardman III, W., Hunt, D.A., (1997) Hum. Pathol., 28, p. 686 Dhanasekaran, S.M., Barrette, T.R., Ghosh, D., (2001) Nature, 412, p. 822 Swinnen, J.V., Roskams, T., Joniau, S., (2002) Int. J. Cancer, 98, p. 19 Innocenzi, D., Alo, P.L., Balzani, A., (2003) J. Cutan. Pathol., 30, p. 23 Rossi, S., Graner, E., Febbo, P., (2003) Mol. Cancer Res., 1, p. 707 Takahiro, T., Shinichi, K., Toshimitsu, S., (2003) Clin. Cancer Res., 9, p. 2204 Visca, P., Sebastiani, V., Botti, C., (2004) Anticancer Res., 24, p. 4169 Kapur, P., Rakheja, D., Roy, L.C., (2005) Mod. Pathol., 18, p. 1107 Van De Sande, T., Roskams, T., Lerut, E., (2005) J. Pathol., 206, p. 214 Rossi, S., Ou, W., Tang, D., (2006) J. Pathol., 209, p. 369 Dowling, S., Cox, J., Cenedella, R.J., (2009) Lipids, 44, p. 489 Furuya, Y., Akimoto, S., Yasuda, K., (1997) Anticancer Res., 17, p. 4589 Pizer, E.S., Chrest, F.J., Digiuseppe, J.A., (1998) Cancer Res., 58, p. 4611 Li, J.N., Gorospe, M., Chrest, F.J., (2001) Cancer Res., 61, p. 1493 Zhou, W., Han, W.F., Landree, L.E., (2007) Cancer Res., 67, p. 2964 Kridel, S.J., Axelrod, F., Rozenkrantz, N., (2004) Cancer Res., 64, p. 2070 Carvalho, M.A., Zecchin, K.G., Seguin, F., (2008) Int. J. Cancer, 123, p. 2557 Zecchin, K.G., Rossato, F.A., Raposo, H.F., (2010) Lab. Invest., , DOI: 10.1038/labinvest.2010.157 Swinnen, J.V., Van Veldhoven, P.P., Timmermans, L., (2003) Biochem. Biophys. Res. Commun., 302, p. 898 Catharino, R.R., Haddad, R., Cabrini, L.G., (2005) Anal. Chem., 77, p. 7429 Yang, L., Bennett, R., Strum, J., (2009) Anal. Bioanal. Chem., 393, p. 643 Fenn, J.B., Mann, M., Meng, C.K., (1989) Science, 246, p. 64 Catharino, R.R., Milagre, H.M.S., Saraiva, A.S., (2007) Energy Fuels, 21, p. 3698 Ferreira, C.R., Souza, G., Riccio, M.F., (2009) Rapid Commun. Mass Spectrom., 23, p. 1313 Santos, L.S., Catharino, R.R., Aguiar, C.L., (2006) J. Radioanal. Nucl. Chem., 269, p. 505 Martin, E.B., Morris, A.J., Zhang, J., (1996) IEE Proc. - Control Theory and Applications, 143, p. 132 Sumner, L.W., Mendes, P., Dixon, R.A., (2003) Phytochemistry, 62, p. 817 Ferreira, C.R., Saraiva, A.S., Catharino, R.R., (2010) J. Lipid Res., , DOI: 10.1194/jlr.D001768 Knowles, L.M., Axelrod, F., Browne, C.D., (2004) J. Biol. Chem., 279, p. 30540 Abou-Khalil, S., Abou-Khalil, W.H., Planas, L., (1985) Biochem. Biophys. Res. Commun., 127, p. 1039 Bligh, E.G., Dyer, W.J., (1959) Can. J. Biochem. Physiol., 37, p. 911 Schrauwen, P., Saris, W.H.M., Hesselink, M.K.C., (2001) FASEB J, 15, p. 2497 De Freitas, E.R.L., Soares, P.R.O., Santos, R.D., (2008) J. Nanosci. Nanotechnol., 8, p. 2385 Liu, J., Shimizu, K., Kondo, R., (2009) Chem. Biodivers., 6, p. 503