This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hardy, S. Articles by Prentki, M. Search for Related Content PubMed PubMed Citation Articles by Hardy, S. Articles by Prentki, M.

Oleate Activates Phosphatidylinositol 3-Kinase and Promotes Proliferation and Reduces Apoptosis of MDA-MB-231 Breast Cancer Cells, Whereas Palmitate Has Opposite Effects¹

Molecular Nutrition Unit, Centre de Recherche du Centre Hospitalier de l’Université de Montréal and Institut du Cancer de Montréal [S. H., Y. L., M. P.], and Departments of Microbiology and Immunology [Y. L.] and Nutrition and Biochemistry [M. P.], Université de Montréal, Montréal, Québec, H2L 4M1 Canada

Epidemiological studies and experiments using animal models and cultured breast cancer cells have suggested that a high intake of dietary fat could increase breast cancer risk. Little is known about the biochemical pathways by which various free fatty acids (FFAs) influence breast cancer cell proliferation and apoptosis. The present study was designed to investigate the effects of the two most abundant circulating FFAs, oleate and palmitate, on established human breast cancer cell lines after a short period of serum starvation. The unsaturated FFA oleate (C:18:1) stimulated cell proliferation, whereas the saturated FFA palmitate (C:16) dose dependently inhibited it. The half maximal effective concentrations of oleate and palmitate in the presence of albumin were 5 and 25 µM, respectively. The growth-inhibitory effect of palmitate in MDA-MB-231 cells was related to the induction of apoptosis as indicated by morphological and biochemical criteria. Moreover, oleate protected cells against the proapoptotic action of palmitate. Oleate and palmitate increased and decreased phophatidylinositol 3-kinase (PI3-K) activity, respectively, and the actions of the two FFAs on the enzyme were antagonistic. The PI3-K inhibitors wortmannin and LY294002 completely blocked the proliferative action of oleate. 2-Bromopalmitate, a nonmetabolizable analogue, did not affect MDA-MB-231 cell proliferation, suggesting that palmitate must be metabolized to exert its effect. Thus, various types of fatty acids are not equivalent with respect to their actions on breast cancer cell proliferation and apoptosis. The results support the concept that PI3-K is implicated in the control of breast cancer cell growth by FFAs and that PI3-K may provide a link between fat and cancer. The data are also consistent with the view that the type of FFA and their ratios in the diet in addition to the total amount of fat influence mammary carcinogenesis.

This article has been cited by other articles:

				C. M. Paton and J. M. Ntambi Biochemical and physiological function of stearoyl-CoA desaturase Am J Physiol Endocrinol Metab, July 1, 2009; 297(1): E28 - E37. [Abstract] [Full Text] [PDF]

				L. A. Stoddart, N. J. Smith, and G. Milligan International Union of Pharmacology. LXXI. Free Fatty Acid Receptors FFA1, -2, and -3: Pharmacology and Pathophysiological Functions Pharmacol. Rev., December 1, 2008; 60(4): 405 - 417. [Abstract] [Full Text] [PDF]

				K. Larade, Z. Jiang, Y. Zhang, W. Wang, S. Bonner-Weir, H. Zhu, and H. F. Bunn Loss of Ncb5or Results in Impaired Fatty Acid Desaturation, Lipoatrophy, and Diabetes J. Biol. Chem., October 24, 2008; 283(43): 29285 - 29291. [Abstract] [Full Text] [PDF]

				M. Prentki and S. R. M. Madiraju Glycerolipid Metabolism and Signaling in Health and Disease Endocr. Rev., October 1, 2008; 29(6): 647 - 676. [Abstract] [Full Text] [PDF]

				V. Koshkin, F. F. Dai, C. A. Robson-Doucette, C. B. Chan, and M. B. Wheeler Limited Mitochondrial Permeabilization Is an Early Manifestation of Palmitate-induced Lipotoxicity in Pancreatic {beta}-Cells J. Biol. Chem., March 21, 2008; 283(12): 7936 - 7948. [Abstract] [Full Text] [PDF]

				E. Lai, G. Bikopoulos, M. B. Wheeler, M. Rozakis-Adcock, and A. Volchuk Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic {beta}-cells Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E540 - E550. [Abstract] [Full Text] [PDF]

				S. M. Turpin, G. I. Lancaster, I. Darby, M. A. Febbraio, and M. J. Watt Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1341 - E1350. [Abstract] [Full Text] [PDF]

				Y. Wei, D. Wang, F. Topczewski, and M. J. Pagliassotti Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E275 - E281. [Abstract] [Full Text] [PDF]

				D. Wang, Y. Wei, and M. J. Pagliassotti Saturated Fatty Acids Promote Endoplasmic Reticulum Stress and Liver Injury in Rats with Hepatic Steatosis Endocrinology, February 1, 2006; 147(2): 943 - 951. [Abstract] [Full Text] [PDF]

				A. M. Kleinfeld and C. Okada Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing J. Lipid Res., September 1, 2005; 46(9): 1983 - 1990. [Abstract] [Full Text] [PDF]

				N. Scaglia and R. A. Igal Stearoyl-CoA Desaturase Is Involved in the Control of Proliferation, Anchorage-independent Growth, and Survival in Human Transformed Cells J. Biol. Chem., July 8, 2005; 280(27): 25339 - 25349. [Abstract] [Full Text] [PDF]

				S. Katsuma, N. Hatae, T. Yano, Y. Ruike, M. Kimura, A. Hirasawa, and G. Tsujimoto Free Fatty Acids Inhibit Serum Deprivation-induced Apoptosis through GPR120 in a Murine Enteroendocrine Cell Line STC-1 J. Biol. Chem., May 20, 2005; 280(20): 19507 - 19515. [Abstract] [Full Text] [PDF]

				S. Hardy, G. G. St-Onge, E. Joly, Y. Langelier, and M. Prentki Oleate Promotes the Proliferation of Breast Cancer Cells via the G Protein-coupled Receptor GPR40 J. Biol. Chem., April 8, 2005; 280(14): 13285 - 13291. [Abstract] [Full Text] [PDF]

				M. Miyazaki, A. Dobrzyn, W. C. Man, K. Chu, H. Sampath, H.-J. Kim, and J. M. Ntambi Stearoyl-CoA Desaturase 1 Gene Expression Is Necessary for Fructose-mediated Induction of Lipogenic Gene Expression by Sterol Regulatory Element-binding Protein-1c-dependent and -independent Mechanisms J. Biol. Chem., June 11, 2004; 279(24): 25164 - 25171. [Abstract] [Full Text] [PDF]

				W. Zhang, C. Wang, C. Qin, T. Wood, G. Olafsdottir, R. Welti, and X. Wang The Oleate-Stimulated Phospholipase D, PLD{delta}, and Phosphatidic Acid Decrease H2O2-Induced Cell Death in Arabidopsis PLANT CELL, October 1, 2003; 15(10): 2285 - 2295. [Abstract] [Full Text] [PDF]

				W. El-Assaad, J. Buteau, M.-L. Peyot, C. Nolan, R. Roduit, S. Hardy, E. Joly, G. Dbaibo, L. Rosenberg, and M. Prentki Saturated Fatty Acids Synergize with Elevated Glucose to Cause Pancreatic {beta}-Cell Death Endocrinology, September 1, 2003; 144(9): 4154 - 4163. [Abstract] [Full Text] [PDF]

				S. Hardy, W. El-Assaad, E. Przybytkowski, E. Joly, M. Prentki, and Y. Langelier Saturated Fatty Acid-induced Apoptosis in MDA-MB-231 Breast Cancer Cells: A ROLE FOR CARDIOLIPIN J. Biol. Chem., August 22, 2003; 278(34): 31861 - 31870. [Abstract] [Full Text] [PDF]

				L. L. Listenberger, X. Han, S. E. Lewis, S. Cases, R. V. Farese Jr., D. S. Ory, and J. E. Schaffer Triglyceride accumulation protects against fatty acid-induced lipotoxicity PNAS, March 18, 2003; 100(6): 3077 - 3082. [Abstract] [Full Text] [PDF]