Effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells

被引:38
作者
Zhao, Lingqin [1 ]
Shou, Huafeng [1 ]
Chen, Lu [1 ]
Gao, Wen [1 ]
Fang, Chenyan [2 ]
Zhang, Ping [1 ]
机构
[1] Zhejiang Canc Hosp, Dept Gynecol Oncol, 1 East Banshan Rd, Hangzhou 310022, Zhejiang, Peoples R China
[2] Zhejiang Chinese Med Univ, Hangzhou 310051, Zhejiang, Peoples R China
关键词
ginsenoside Rg3; invasion and metastasis; methylation; deacetylation; ovarian cancer; HISTONE; METHYLATION; LANGUAGE; P16; EXPRESSION; RISK; P53;
D O I
10.3892/or.2019.7115
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetic modifications are closely related to oncogene activation and tumor suppressor gene inactivation. The aim of this study was to determine the effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells. Cell proliferation, metastasis, invasion and apoptosis were respectively determined using Cell Counting Kit-8 (CCK-8), wound healing, Transwell and flow cytometric assays. Methylation levels were determined using methylation specific PCR (MSP). Related-factor expression was detected by conducting real-time-qPCR (RT-qPCR) and western blotting. The results revealed that cell proliferation was inhibited by ginsenoside Rg3 (0, 25, 50, 100 and 200 mu g/ml) in a time-dependent manner (12, 24 and 48 h). Ginsenoside Rg3 (50, 100 and 200 mu g/ml) was selected to treat cells in various experiments. When ovarian cells were treated with ginsenoside Rg3, cell apoptosis was observed to be promoted, while cell metastasis and invasion were inhibited at 48 h. The results of the present study revealed that in the promoter regions of p53, p16 and hMLH1, the methylation levels decreased, while the mRNA and protein levels significantly increased. The activities of DNMTs and mRNA as well as protein levels of DNMT1, DNMT3a and DNMT3b were decreased by Rg3. The data also demonstrated that the mRNA and protein levels of acetyl-H3 K14/K9 and acetyl-H4 K12/K5/K16 were increased by Rg3. Hence, ginsenoside Rg3 inhibited ovarian cancer cell viability, migration and invasion as well as promoted cell apoptosis.
引用
收藏
页码:3209 / 3218
页数:10
相关论文
共 32 条
[1]   HDAC inhibitors enhance the immunotherapy response of melanoma cells [J].
Booth, Laurence ;
Roberts, Jane L. ;
Poklepovic, Andrew ;
Kirkwood, John ;
Dent, Paul .
ONCOTARGET, 2017, 8 (47) :83155-83170
[2]   Histone Deacetylase (HDAC) Inhibition Induces IkB Kinase (IKK)-dependent Interleukin-8/CXCL8 Expression in Ovarian Cancer Cells [J].
Gatla, Himavanth R. ;
Zou, Yue ;
Uddin, Mohammad M. ;
Singha, Bipradeb ;
Bu, Pengli ;
Vancura, Ales ;
Vancurova, Ivana .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (12) :5043-5054
[3]   Aberrant p15, p16, p53, and DAPK Gene Methylation in Myelomagenesis: Clinical and Prognostic Implications [J].
Geraldes, Catarina ;
Goncalves, Ana Cristina ;
Cortesao, Emilia ;
Pereira, Marta Isabel ;
Roque, Adriana ;
Paiva, Artur ;
Ribeiro, Leticia ;
Nascimento-Costa, Jose Manuel ;
Sarmento-Ribeiro, Ana Bela .
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, 2016, 16 (12) :713-+
[4]   Panax ginseng pharmacology: A nitric oxide link? [J].
Gillis, CN .
BIOCHEMICAL PHARMACOLOGY, 1997, 54 (01) :1-8
[5]  
Gurard-Levin Zachary A, 2014, F1000Prime Rep, V6, P76, DOI 10.12703/P6-76
[6]   Linking the epigenetic 'language' of covalent histone modifications to cancer [J].
Hake, SB ;
Xiao, A ;
Allis, CD .
BRITISH JOURNAL OF CANCER, 2004, 90 (04) :761-769
[7]   The ARID1A, p53 and β-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium [J].
Heckl, Marlene ;
Schmoeckel, Elisa ;
Hertlein, Linda ;
Rottmann, Miriam ;
Jeschke, Udo ;
Mayr, Doris .
PLOS ONE, 2018, 13 (02)
[8]  
Henderson JT, 2018, 1705231EF1 AG HEALTH
[9]   Methylation levels of P16 and TP53 that are involved in DNA strand breakage of 16HBE cells treated by hexavalent chromium [J].
Hu, Guiping ;
Li, Ping ;
Li, Yang ;
Wang, Tiancheng ;
Gao, Xin ;
Zhang, Wenxiao ;
Jia, Guang .
TOXICOLOGY LETTERS, 2016, 249 :15-21
[10]  
Ibanez de Caceres I, 2004, CANCER RES, V64, P6476