The effect of unsaturated fatty acids on membrane composition and signal transduction in HT-29 human colon cancer cells.
The objective of the present study was to investigate the effect of membrane fatty acid (FA) composition on the activity of phospholipase C (PLC) in HT-29 human colon cancer cells. The membrane FA composition was altered by supplementing cultured cells with FAs of different composition. The FAs were stearic acid (18:0; SA), gamma linolenic acid (18:3 omega 6; gamma LnA); alpha linolenic acid (18:3 omega 3; alpha LnA;); eicosapentaenoic acid (20:5 omega 3; EPA) and docosahexaenoic acid (22:6 omega 3; DHA). The fatty acids were supplemented as a FA/BSA complex. Cells supplemented with SA served as the control. Tumor growth was followed by counting the number of cells in culture. The results indicate that polyunsaturated fatty acid (PUFA) supplementation had no consistent effect on tumor growth from 1 day to another throughout the 15 days of growth. The fatty acid composition of membranes indicates that cells incorporated and modified the supplemented fatty acids by desaturation, elongation and retroconversion. The unsaturation index (UI) of membranes of cells supplemented with EPA and DHA was higher than other groups. PLC activity; measured in the absence of GTP gamma(S) in the assay mixture; was not influenced by membrane FA modification. However, in the presence of GTP gamma(S) PLC of cells supplemented with 18:3(omega 6) was the lowest among the groups. It has been shown that 18:3(omega 6) accumulated the most in the phosphatidylethanolamine (PE) fraction. There was a negative correlation between the activity of PLC in the presence of G protein activation and PE 18:3 (omega 6) content without affecting UI. It was concluded that G protein may be sensitive to the level of 18:3(omega 6) content and not to the general fluidity of the membranes.
Awad
A B
AB
Nutrition Program, State University of New York at Buffalo 14214, USA.
Young
A L
AL
Fink
C S
CS
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000473:pathology*; D004041:Dietary Fats / Q000009:adverse effects / Q000145:classification; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000032:analysis / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013229:Stearic Acids / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D017962:alpha-Linolenic Acid / Q000494:pharmacology; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D013229:Stearic Acids; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D012710:Serum Albumin, Bovine; C031183:stearic acid; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase