Cis 9, trans 11- and trans 10, cis 12-conjugated linoleic acid isomers induce apoptosis in cultured SW480 cells.
Dietary conjugated linoleic acid (CLA) has been shown to reduce colon tumor incidence in rodents by mechanisms probably involving apoptosis. The aim of this study was to evaluate the effects of three commercial CLA preparations (pure c9, t11-CLA, pure t10, c12-CLA and a CLA mixture, containing 29.5% c9, t11 and 29% t10, c12-CLA) on caspase-dependent apoptosis in colon SW480 tumor cells. After 4 days incubation, all CLA-treated cells displayed an increase in caspase 3 (27-34%) and caspase 9 activities (37-47%), cleavage of pro-caspase 3 (32 kDa) to 17 and 12 kDa subunits, increased membrane annexin V levels and reduced expression of bcl-2 compared with untreated controls. Cytosolic cytochrome c was increased (p < 0.05) by all CLA preparations, with the t10, c12-CLA isomer being the most potent. The data indicate that t10, c12-CLA may be the more biologically active isomer for inhibition of colon tumor cell proliferation in vitro.
Miller
Aine
A
School of Biotechnology, Dublin City University, Dublin 9, Ireland.
Stanton
Catherine
C
Devery
Rosaleen
R
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003574:Cytochrome c Group / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D008041:Linoleic Acids / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C506592:APAF1 protein, human; D017304:Annexin A5; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D004273:DNA, Neoplasm; D008041:Linoleic Acids; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases