Analysis Center, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.
Anticancer Agents Med Chem. 2019;19(3):330-336. doi: 10.2174/1871520618666181018143026.
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.
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 omega-3 PUFAs.
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), catalyzing the generation of 5hmC, was also evaluated by quantitative real-time PCR.
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 close to NC group and was significantly higher than that in the CRC group. Consistent alteration pattern of TET1 expressions in mRNA was also observed in the tested groups of rats.
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.
ω-3 多不饱和脂肪酸（ω-3PUFAs）具有显著的多种抗肿瘤作用。然而，表观遗传 DNA 羟甲基化是否参与 ω-3PUFAs 的抗癌过程尚不清楚。
阐述 ω-3PUFAs 的抗肿瘤作用与 DNA 去甲基化途径之间的相互关系，为深入了解 ω-3PUFAs 的抗癌机制提供坚实的基础。
采用 N-甲基-N-亚硝脲诱导大鼠结直肠癌（CRC）模型，诱导过程中用 ω-3PUFAs 处理其对照。不同处理组大鼠（正常对照组[NC]、结直肠癌模型组[CRC]和 ω-3PUFAs 药物组[MG]）的血液样本作为实验材料。采用 LC-MS/MS 定量检测基因组 5-羟甲基胞嘧啶（5hmC）含量，并用实时定量 PCR 评估十-十一易位双加氧酶 1（TET1）的表达，该酶催化 5hmC 的生成。
与 CRC 组相比，MG 组的肿瘤发生率较低，肿瘤体积较小，表明 ω-3PUFAs 具有有效的抗癌作用。由于 CRC 的形成，CRC 组的 5hmC 水平与 NC 组相比显著下降。值得注意的是，MG 组的 5hmC 百分比显著增加，接近 NC 组，明显高于 CRC 组。在检测的大鼠组中，TET1 表达的 mRNA 也观察到了一致的变化模式。
ω-3PUFAs 的抗癌作用与全球 5hmC 积累和 TET1 表达呈正相关，表明 DNA 羟甲基化途径实际上参与了 ω-3PUFAs 的抗癌过程。
