The 10t,12c isomer of conjugated linoleic acid inhibits fatty acid synthase expression and enzyme activity in human breast, colon, and prostate cancer cells.
The objective of this study was to determine whether downregulation of fatty acid synthase (FAS) expression and/or inhibition of its activity by the two major CLA isomers, 10t,12c and 9c,11t CLA, could contribute to their inhibitory effect on the growth of human breast (MCF-7), colon (HT-29) and prostate (LNCaP) cancer cell lines. We first confirmed and extended the results of others showing that the inhibitory action of CLA on proliferation is dependent on the cell type as well as the structure of the isomer, the 10,12 isomer being a more potent inhibitor than the 9,11 isomer in the concentration range 25-100 microM. By Western analysis, we showed that 10,12 CLA downregulated FAS expression in all of the cell lines in a concentration-dependent manner, but the 9,11 isomer had no effect. Both isomers inhibited FAS enzyme activity, but 10,12 CLA was again more potent than the 9,11 isomer. Our results suggest that downregulation of FAS by 10,12 CLA, but not by the 9,11 isomer, as well as inhibition of FAS enzyme activity by both isomers, may contribute to growth inhibition of cancer cells but only at relatively high concentrations.
Lau
Dominic S Y
DS
University of Toronto, Toronto, Ontario, Canada.
Archer
Michael C
MC
D000970:Antineoplastic Agents; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D044243:Linoleic Acids, Conjugated; D064429:Fatty Acid Synthases