Background: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have significant multiple antitumor
roles. However, whether epigenetic DNA hydroxymethylation enrolls in the anticancer process of omega-
3 PUFAs is still not clear yet.
Objective: To expound the interaction between the 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
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), which
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 the NC group. Notably, 5hmC percentage in MG
group remarkably increased to close to NC group and was significantly higher than that in the 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.
Keywords: Omega-3 polyunsaturated fatty acids, Ten-eleven translocation dioxygenase 1, 5-hydroxymethylcytosine, DNA hydroxymethylation, Colorectal cancer
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