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

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 epigenet...

Full description

Bibliographic Details
Main Authors: Yasi Xu, Dan Su, Lucheng Zhu, Shirong Zhang, Shenglin Ma, Kan Wu, Qiang Yuan, Nengming Lin
Format: Article
Language:English
Published: BMC 2018-05-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13048-018-0412-1
_version_ 1797973056176521216
author Yasi Xu
Dan Su
Lucheng Zhu
Shirong Zhang
Shenglin Ma
Kan Wu
Qiang Yuan
Nengming Lin
author_facet Yasi Xu
Dan Su
Lucheng Zhu
Shirong Zhang
Shenglin Ma
Kan Wu
Qiang Yuan
Nengming Lin
author_sort Yasi Xu
collection DOAJ
description 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.
first_indexed 2024-04-11T03:58:11Z
format Article
id doaj.art-23b80899f04e470987d72ea6fdae0a4b
institution Directory Open Access Journal
issn 1757-2215
language English
last_indexed 2024-04-11T03:58:11Z
publishDate 2018-05-01
publisher BMC
record_format Article
series Journal of Ovarian Research
spelling doaj.art-23b80899f04e470987d72ea6fdae0a4b2023-01-02T00:02:09ZengBMCJournal of Ovarian Research1757-22152018-05-011111810.1186/s13048-018-0412-1S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1Yasi Xu0Dan Su1Lucheng Zhu2Shirong Zhang3Shenglin Ma4Kan Wu5Qiang Yuan6Nengming Lin7Hangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People’s HospitalDepartment of Pathology, Zhejiang Cancer HospitalDepartment of Oncology, Hangzhou Cancer HospitalHangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People’s HospitalHangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People’s HospitalDepartment of Oncology, Hangzhou Cancer HospitalCollege of Pharmaceutical Science, Zhejiang Chinese Medical UniversityHangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People’s HospitalAbstract 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.http://link.springer.com/article/10.1186/s13048-018-0412-1EpigeneticDNA methylationS-allylcysteineOvarian cancer
spellingShingle Yasi Xu
Dan Su
Lucheng Zhu
Shirong Zhang
Shenglin Ma
Kan Wu
Qiang Yuan
Nengming Lin
S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1
Journal of Ovarian Research
Epigenetic
DNA methylation
S-allylcysteine
Ovarian cancer
title S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1
title_full S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1
title_fullStr S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1
title_full_unstemmed S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1
title_short S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1
title_sort s allylcysteine suppresses ovarian cancer cell proliferation by dna methylation through dnmt1
topic Epigenetic
DNA methylation
S-allylcysteine
Ovarian cancer
url http://link.springer.com/article/10.1186/s13048-018-0412-1
work_keys_str_mv AT yasixu sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT dansu sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT luchengzhu sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT shirongzhang sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT shenglinma sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT kanwu sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT qiangyuan sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1
AT nengminglin sallylcysteinesuppressesovariancancercellproliferationbydnamethylationthroughdnmt1