Trans fatty acids affect cellular viability of human intestinal Caco-2 cells and activate peroxisome proliferator-activated receptors.
Trans fatty acids (TFA) are hypothesized to have an impact not only on coronary heart diseases but also on the development of colon cancer. To analyze if TFA exhibit cellular and molecular effects which could be involved in colon tumor progression, cells of the human colorectal adenocarcinoma-derived cell line Caco-2 were treated with various TFA isomers differing in the number and position of trans double bonds. The TFA tested in this study did not increase cellular proliferation but displayed growth-inhibitory effects at concentrations higher than 500 μM. In case of the TFA isomer C18:3 t9, t11, t13, an IC50 value of 23 μM was estimated for cytotoxicity indicating a high cytotoxic potential of this compound. In addition to the cytotoxicity studies, the TFA isomers were tested for their ability to activate peroxisome proliferator-activated receptors (PPAR) by taking advantage of a PPAR-dependent reporter gene assay. In contrast to PPARγ that was not activated by the TFA isomers tested in this study, the substances were shown to moderately activate PPARα, and strong activation was observed for PPARδ. The putative impact of TFA on colon cancer development with respect to PPARδ activation is being discussed.
Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.
Marianne
M
Kloetzel
Anke
A
Ehlers
Birgit
B
Niemann
Thorsten
T
Buhrke
Alfonso
A
Lampen
D018938:Caco-2 Cells / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007536:Isomerism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D044242:Trans Fatty Acids / Q000737:chemistry / Q000494:pharmacology*
D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D044242:Trans Fatty Acids; D007770:L-Lactate Dehydrogenase