title: Upregulation of cellular triacylglycerol - free fatty acid cycling by oleate is associated with long-term serum-free survival of human breast cancer cells.
abstract: We previously showed that exogenous oleate protects human breast cancer cells against palmitate-induced apoptosis in part by increasing esterification of this free fatty acid (FFA) into triacylglycerol (TG). Here, we studied the mechanism whereby oleate protects these cells against apoptosis induced by serum withdrawal. The metabolism of FFA, TG, and glucose, in parallel with long-term cell survival in the absence of serum, was investigated in a panel of human breast cancer cell lines and in nontransformed MCF-10A cells after treatment with exogenous oleate. Short-term (3-24 h) exposure of MDA-MB-231 human breast cancer cells to exogenous oleate resulted in a dose-dependent long-term (10 day) serum-free survival that correlated with the accumulation of TG in lipid droplets and with upregulation of lipolysis. Both effects persisted for several days after oleate removal. Rapid TG lipolysis and FFA re-esterification, supported by high rates of glycolysis that provide the glycerol backbone for TG synthesis, are consistent with the presence of very active TG-FFA cycling in human breast cancer cells. Only the cancer cell lines capable of accumulating TG showed long-term serum-free survival after oleate treatment. The results suggest that upregulation of TG-FFA cycling induced by oleate may be involved in maintenance of human breast cancer cell survival.
authors.affiliation: Molecular Nutrition Unit, Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Montréal, QC, Canada.
authors.forename: Ewa
authors.initials: E
authors.lastname: Przybytkowski
authors.forename: Erik
authors.initials: E
authors.lastname: Joly
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nolan
authors.forename: Serge
authors.initials: S
authors.lastname: Hardy
authors.forename: Ann-Michele
authors.initials: AM
authors.lastname: Francoeur
authors.forename: Yves
authors.initials: Y
authors.lastname: Langelier
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004951:Esterification; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006019:Glycolysis; D006801:Humans; D007700:Kinetics; D008066:Lipolysis; D008954:Models, Biological; D019301:Oleic Acid / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016895:Culture Media, Serum-Free; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D019301:Oleic Acid