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J Ovarian Res. 2018 May 14;11(1):39. doi: 10.1186/s13048-018-0412-1.

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

Author information

1
Hangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, No.261 Huansha Road, Shangcheng District, Hangzhou, 310006, China.
2
College of Pharmaceutical Science, Zhejiang Chinese Medical University, No.548 Binwen Road, Binjiang District, Hangzhou, 310053, China.
3
Department of Pathology, Zhejiang Cancer Hospital, No.38, Guangji Road, Hangzhou, 310022, China.
4
Department of Oncology, Hangzhou Cancer Hospital, No.34, Yanguan Road, Hangzhou, 310002, China.
5
College of Pharmaceutical Science, Zhejiang Chinese Medical University, No.548 Binwen Road, Binjiang District, Hangzhou, 310053, China. 794884530@qq.com.
6
Hangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, No.261 Huansha Road, Shangcheng District, Hangzhou, 310006, China. lnm1013@163.com.

Abstract

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.

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.

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.

KEYWORDS:

DNA methylation; Epigenetic; Ovarian cancer; S-allylcysteine

PMID:
29759079
PMCID:
PMC5952516
DOI:
10.1186/s13048-018-0412-1
[Indexed for MEDLINE]
Free PMC Article

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