Studies On The Regulation Of Conjugated Linoleic Acids On The COX-2 And PPARγ Of Cancer Cells

Conjugated linolei acids (CLAs) comprise a family of positional and geometric isomers of linoleic acid. Initially identified in grilled beef as a potential anti-carcinogen by Pariza a surprising number of health benefits have subsequently been attributed to CLA, including anti-atherogenic, anti-adipogenic, anti-diabetogenic, anti-inflammatory. It was also reported beneficial regulatory effects on immune function, lipid and eicosanoid metabolism, cytokine and immuno-globulin production and can modulate the expression of a number of genes. But the mechanisms are not clear. In the research the effects of conjugated linoleic acids on PPARγ and COX-2 and related signaling protein areto be investgated.Firstly, the anti-proliferative effects of five CLA isomer were detected. We found that all the five isomers could inhibit the proliferation of cancer cells, the inhibitory effects corresponded with isomers, cell type and concentration. Also c9,tll-CLA and t10,c12-CLA induced apoptosis to the Bel7402 cancer cells.Secondly, c9,t11-CLA and t10,c12-CLA could significantly inhbit the expression of COX-2 at the level of mRNA and protein, they could also significanty inhibit the expression of PPARy (mRNA), but the downregulated effect on PPARγ protein lever was not significant. PPARγ agonist - rosiglitazone and COX-2 specific inhibitor NS-398 exhibited inhibitory effects on the proliferation of Bel7402 cells respectively, but combined treatment with the two chemicals didn't increase the inhibitory effects, which indicated that COX-2 and PPARγ share the same downstream pathway. Rosiglitazone also could inhibit the COX-2 protein content. GW9662 coule reverse the downregulated effects of c9,t11-CLA on COX-2 protein, but didn't change the effects of t10,c12-CLA, suggested that PPARγ is a critical point in the mechanism of c9,t11-CLA and may be the upstream regulator of COX-2.Lastly, c9,t11-CLA and t10,c12-CLA significantly downregulated the protein level of phosphored ERK, while the level of total ERK did not change. P38 MAPK pathway was not affected by the two isomers. The protein contents of NFkB and c-myc decreased significantly after CLA treatments.Taken together, CLAs could inhibit the proliferation of cancer cells, induced apoptosis. The mechanisms included COX-2 and PPARγ, but diferrent isomers have diferrent mechanisms. PPARγ is a key point to c9,t11-CLA, while not important to t10,c12-CLA. Signalling proteins ERK, NFkB and oncogene c-myc participate in the process.