Metabolic and growth inhibitory effects of conjugated fatty acids in the cell line HT-29 with special regard to the conversion of t11,t13-CLA

Biochim Biophys Acta. 2011 Dec;1811(12):1070-80. doi: 10.1016/j.bbalip.2011.08.005. Epub 2011 Aug 26.

Abstract

Conjugated fatty acids (CFAs) exhibit growth inhibitory effects on colon cancer in vitro and in vivo. To investigate whether the anticancerogenic potency depends on number or configuration of the conjugated double bonds, the effect of conjugated linoleic acid (CLA; C18:2) isomers and conjugated linolenic acid (CLnA; C18:3) isomers on viability and growth of HT-29 cells were compared. Low concentrations of CLnAs (<10μM) yielded a higher degree of inhibitory effects compared to CLAs (40μM). All trans-CFAs were more effective compared to cis/trans-CFAs as follows: t9,t11,t13-CLnA≥c9,t11,t13-CLnA>t11,t13-CLA≥t9,t11-CLA>c9,t11-CLA. The mRNA expression analysis of important genes associated with fatty acid metabolism showed an absence of ∆5-/∆6-desaturases and elongases in HT-29 cells, which was confirmed by fatty acid analysis. Using time- and dose-dependent stimulation experiments several metabolites were determined. Low concentrations of all trans-CFAs (5-20μM) led to dose-dependent increase of conjugated t/t-C16:2 formed by β-oxidation of C18 CFAs, ranging from 1-5% of total FAME. Importantly, it was found that CLnA is converted to CLA and that CLA is inter-converted (t11,t13-CLA is metabolized to c9,t11-CLA) by HT-29 cells. In summary, our study shows that growth inhibition of human cancer cells is associated with a specific cellular transcriptomic and metabolic profile of fatty acid metabolism, which might contribute to the diversified ability of CFAs as anti-cancer compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / deficiency
  • Acetyltransferases / genetics
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Fatty Acid Desaturases / deficiency
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Elongases
  • Gas Chromatography-Mass Spectrometry
  • Gene Expression
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / metabolism
  • Growth Inhibitors / pharmacology*
  • HT29 Cells
  • Humans
  • Isomerism
  • Linoleic Acids, Conjugated / chemistry
  • Linoleic Acids, Conjugated / metabolism
  • Linoleic Acids, Conjugated / pharmacology*
  • Lipid Metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • alpha-Linolenic Acid / chemistry
  • alpha-Linolenic Acid / metabolism
  • alpha-Linolenic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Growth Inhibitors
  • Linoleic Acids, Conjugated
  • RNA, Messenger
  • alpha-Linolenic Acid
  • 9,11-linoleic acid
  • Fatty Acid Desaturases
  • Acetyltransferases
  • Fatty Acid Elongases