Differential induction of apoptosis and inhibition of the PI3-kinase pathway by saturated, monounsaturated and polyunsaturated fatty acids in a colon cancer cell model.
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.
Engelbrecht
Anna-Mart
AM
Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa. ame@sun.ac.za
Toit-Kohn
Joe-Lin du
JL
Ellis
Beverly
B
Thomas
Mark
M
Nell
Theo
T
Smith
Rob
R
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
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D019869:Phosphatidylinositol 3-Kinases