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学科主题: 临床医学
题名:
Histone deacetylase inhibitors inducing human cervical cancer cell apoptosis by decreasing DNA-methyltransferase 3B
作者: Liu Ning1; Zhao Li-jun1; Li Xiao-ping1; Wang Jian-liu1; Chai Guo-lin2; Wei Li-hui1
关键词: histone deacetylase inhibitors ; human cervical cancer ; apoptosis ; DNA-methyltransferase 3B ; Trichostatin A ; DNA methyl transferase
刊名: CHINESE MEDICAL JOURNAL
发表日期: 2012-09-20
DOI: 10.3760/cma.j.issn.0366-6999.2012.18.014
卷: 125, 期:18, 页:3273-3278
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, General & Internal
研究领域[WOS]: General & Internal Medicine
关键词[WOS]: SUBEROYLANILIDE HYDROXAMIC ACID ; ACUTE MYELOID-LEUKEMIA ; TRANSCRIPTION ; THERAPY ; DNMT1
英文摘要:

Background Histone deacetylase (HDAC) inhibitors are a group of small chemical molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have multiple biological effects such as cell cycle arrest, apoptosis, cell differentiation and auotophagy. At molecular level, HDAC inhibitors cause histone and nonhistone acetylation and induce gene expression. HDAC inhibitors are widely used in cancer therapy because of its function of inducing apoptosis. However, the mechanisms of apoptosis effect are not fully understood. TSA is a classical HDAC inhibitor and widely used in epigenetic and anti-cancer research. In this study, we selected Trichostatin A (TSA) to investigate the mechanisms of HDAC inhibitors apoptotic effect on cancer cells.

Methods Cervical cancer cell lines such as Hela, Caski and normal human keratinocyte line HaCaT were treated with various concentrations of TSA. Crystal violent assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine cell number. PARP cleavage and FITC-AnexinV were performed to determine apoptosis. DNA-methyltransferase (DNMT)1, DNMT3A and DNMT3B were determined by regular PCR, qPCR and Western Blotting. Small interfering RNA (SiRNAi) was used to knock down DNMT3B.

Results HDAC inhibitors only induce cervical cancer cell apoptosis. At 1 mu mol/L of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal cells, HDAC inhibitors have no cytotoxic effect at therapeutic dosage, (90.0+/-8.4)% of normal cell survive after treated with 1 mu mol/L of TSA. We compared 1 mu mol/L group with untreated control with t-test. There was no significance between 1 mu mol/L group and untreated control for normal cell (P >0.05). HDAC inhibitors decreased DNMT3B in cancer cell but not in normal cell. Manually knock-down of DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and Caski cell went apoptosis after deprived of DNMT3B.

Conclusions DNMT3B was essential to cervical cancer cell survival. Down-regulated DNMT3B by HDAC inhibitors may play an important role in the toxicity of HDAC inhibitors on cervical cancer cells. Chin Med J 2012;125(18):3273-3278

语种: 英语
所属项目编号: 30571938 ; 985-2-015-24
项目资助者: National Natural Science Foundation of China ; "985" Project of the Peking University Health Science Center ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
WOS记录号: WOS:000311264900014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55239
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Dept Obstet & Gynecol, Beijing 100044, Peoples R China
2.China Japan Friendship Hosp, Dept Hematol, Beijing 100029, Peoples R China

Recommended Citation:
Liu Ning,Zhao Li-jun,Li Xiao-ping,et al. Histone deacetylase inhibitors inducing human cervical cancer cell apoptosis by decreasing DNA-methyltransferase 3B[J]. CHINESE MEDICAL JOURNAL,2012,125(18):3273-3278.
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