S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1

S-烯丙基半胱氨酸通过 DNMT1 的 DNA 甲基化抑制卵巢癌细胞增殖

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作者:Yasi Xu, Dan Su, Lucheng Zhu, Shirong Zhang, Shenglin Ma, Kan Wu, Qiang Yuan, Nengming Lin

Background

The anti-tumor effects of S-allylcysteine (SAC), a water-soluble garlic derivative, on human ovarian cancer cells have been previous studied in vitro and in vivo models but the precise epigenetic molecular mechanisms are still unclear. This study aimed to investigate the epigenetic mechanism of SAC.

Conclusion

Our data indicated the potential therapeutic effects of SAC on the human ovarian carcinoma cell line A2780 in vitro. The epigenetic mechanism of action of SAC may have important implications for epigenetic therapy.

Methods

Human epithelial ovarian cancer cell line A2780 was selected. Cell proliferation and cell cycle was analyzed. DNA methylation, DNA methyltransferase (DNMT) activity, tumor suppressor gene expressions, as well as protein expression were analyzed.

Results

SAC could inhibit the proliferation of A2780 cells in dose- and time-dependent manners (the IC50 was 16.25 mmol/L and 5.25 mmol/L at 48 h and 72 h). Treatment of A2780 cells with SAC resulted in G1/S phase arrest. SAC treatment decreased global DNA methylation levels in A2780 cells in a dose-dependent manner. SAC decreased the levels of 5-methylcytosine, DNMT activity, messenger RNA (mRNA) and protein levels of DNMT1. Additionally, SAC treatment resulted in re-expression of the mRNA and proteins of silenced tumor suppressor gene CDKN1A accompany with reduced cell division control 2 expression.

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