The anticancer role of omega-3 polyunsaturated fatty acids was closely associated with the increase of genomic DNA hydroxymethylation.

BACKGROUND: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have significant multiple anti-tumor roles. However, whether epigenetic DNA hydroxymethylation enroll in the anticancer process of omega-3 PUFAs is still not clear yet.

OBJECTIVE: To expound the interaction between anti-tumor role of omega-3 PUFAs and the DNA demethylation pathway and thus provide a firm foundation for deepening our understanding on anticancer mechanism of omega-3 PUFAs.

METHODS: Colorectal cancer (CRC) model rats were induced to generate tumor by N-methyl-N-nitrosourea and their counterparts treated with omega-3 PUFAs during the induction. The blood samples from different treatment groups of rats [normal control group (NC), colorectal cancer model group (CRC) and omega-3 PUFAs medication group (MG)] were used as experimental materials. Genomic 5-hydroxymethylocytosine (5hmC) content was quantified using LC-MS/MS, and the expression of ten-eleven translocation dioxygenase 1 (TET1), who catalyzed the generation of 5hmC, was also evaluated by quantitative real-time PCR and western-blotting.

RESULTS: We observed lower tumor incidence and small tumor size in MG group when compared with CRC group, supporting the effective anticancer role of omega-3 PUFAs. Due to the formation of CRC, 5hmC level was dramatically dropped in CRC group when compared with NC group. Notably, 5hmC percentage in MG group remarkably increased to close to NC group and was significantly higher than that in CRC group. Consistent alteration pattern of TET1 expressions in mRNA and protein levels was also observed in the tested groups of rats.

CONCLUSION: The anticancer effect of omega-3 PUFAs was positively correlated with global 5hmC accumulation and TET1 expression, suggesting DNA hydroxymethylation pathway was factually involved in the anticancer process of omega-3 PUFAs.