Effect of branched-chain fatty acids on fatty acid biosynthesis of human breast cancer cells.
This paper describes the antitumoral activity of branched-chain fatty acid (BCFA) in human breast cancer cells with an emphasis on its effect on fatty acid biosynthesis. First, the relationship between chain-length and antitumoral activity was studied. The highest activity was observed with iso-16:0, and the activity decreased with increase or decrease of the chain-lengths from C16:0. Anteiso-BCFA, as well as iso-series, was cytotoxic to the breast cancer cells. Cytotoxicity of BCFA was comparable to that of conjugated linoleic acid known as antitumoral fatty acid. Incubation of breast cancer cells with BCFA (13-methyltetradecanoic acid) significantly reduced the [14C] acetate incorporation into free fatty acid and fatty acid esters, showing the inhibition of fatty acid biosynthesis by BCFA. Examination of substrate level effect found that BCFA slightly inhibited fatty acid synthetase and acetyl-CoA carboxylase, and significantly the glucose-6-phosphate dehydrogenase which was the main NADPH generating system in breast cancer cells. The present study thus suggests that BCFA synthetically lowers the fatty acid biosynthesis by reducing the precursors, in addition to its direct inhibitory effect on fatty acid synthetase.
Wongtangtintharn
Sawitree
S
United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24, Korimoto, Kagoshima 890-0065, Japan.
Oku
Hirosuke
H
Iwasaki
Hironori
H
Toda
Takayoshi
T
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D005227:Fatty Acids / Q000096:biosynthesis* / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology; D019814:Myristic Acid / Q000494:pharmacology; D009227:Myristic Acids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D044243:Linoleic Acids, Conjugated; D009227:Myristic Acids; D019814:Myristic Acid; D005954:Glucosephosphate Dehydrogenase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; C027331:13-methyltetradecanoic acid