title: Differential induction of apoptosis and inhibition of the PI3-kinase pathway by saturated, monounsaturated and polyunsaturated fatty acids in a colon cancer cell model.
abstract: Although numerous studies have shown that certain long chain fatty acids can induce apoptosis in cancer cells, the molecular mechanisms for this phenomenon are still poorly elucidated. The phosphoinositide 3-kinase (PI3-kinase) signaling pathway plays a pivotal role in the regulation of cell growth and can also contribute to tumorigenesis and cancer progression. The aims of the present study were three fold: (i) to investigate the potential chemopreventative/antiproliferative effect of various fatty acids in colon cancer cells (CaCo-2 cells) and normal colon epithelium cells (NCM460 cells); (ii) to investigate the mechanisms by which incubation with various fatty acids influences the PI3-kinase pathway in CaCo-2 cells; and (iii) to evaluate apoptosis in our cell model. Although all the fatty acids increased the viability of normal (NCM460) cells, only docosahexaenoic acid (DHA) significantly reduced cell viability and induced apoptosis in the cancer (CaCo-2) cells. Our results indicate that DHA is an effective chemotherapeutic agent to induce apoptosis in cancer cells and that this effect is mediated by the PI3-kinase signaling pathway.
authors.affiliation: Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa. ame@sun.ac.za
authors.forename: Anna-Mart
authors.initials: AM
authors.lastname: Engelbrecht
authors.forename: Joe-Lin du
authors.initials: JL
authors.lastname: Toit-Kohn
authors.forename: Beverly
authors.initials: B
authors.lastname: Ellis
authors.forename: Mark
authors.initials: M
authors.lastname: Thomas
authors.forename: Theo
authors.initials: T
authors.lastname: Nell
authors.forename: Rob
authors.initials: R
authors.lastname: Smith
mesh_terms: D017209:Apoptosis; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004281:Docosahexaenoic Acids / Q000737:chemistry; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D019869:Phosphatidylinositol 3-Kinases