Dietary polyunsaturated fatty acids affect PPARγ promoter methylation status and regulate the PPARγ/COX2 pathway in some colorectal cancer cell lines

Background Promoter methylation silencing of peroxisome proliferator-activated receptor gamma (PPAR gamma) and dysregulation of the PPAR gamma/COX2 axis contribute to colorectal cancer (CRC) pathogenesis. This study investigated for the first time the effects of dietary polyunsaturated fatty acids (PUFAs) on promoter methylation of PPAR gamma and the PPAR gamma/COX2 axis in five CRC cell lines. Methods Five CRC cell lines (SW742, HCT116, Caco2, LS180, and HT29/219) were treated with 100 mu M of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or linoleic acid (LA). The methylation patterns of the four regions within the PPAR gamma promoter were determined using methylation-specific PCR (MSP). Additionally, the mRNA expression levels of PPAR gamma and COX2 were examined using RT-qPCR. Results Our results showed that M3 segment within the PPAR gamma promoter was hemimethylated in SW742 cells, whereas other cell lines remained unmethylated in this region. The M4 region was hemimethylated in all the CRC cell lines. Of all PUFAs, DHA demethylated the M3 region of the PPAR gamma promoter in SW742 cells and the M4 region in Caco2 cells. Functionally, these changes were accompanied by significant upregulation of PPAR gamma in SW742 (9.22-fold; p = 0.01) and Caco2 cells (8.87-fold; p = 0.04). Additionally, COX2 expression was significantly downregulated in all CRC cell lines after exposure to PUFAs (p < 0.05). Conclusions This study demonstrated that PUFAs, particularly DHA, altered PPAR gamma promoter methylation and expression, as well as modulated the PPAR gamma/COX2 axis in CRC cells in a cell type-dependent manner. DHA was more effective than the other PUFAs in regulating PPAR gamma promoter methylation. Our results highlight the potential clinical use of PUFAs in CRC treatment.