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学科主题: 基础医学
题名:
HDAC Inhibitors Act with 5-aza-2 ′-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells
作者: Chai, Guolin1; Li, Lian1; Zhou, Wen1; Wu, Lipeng1; Zhao, Ying1; Wang, Donglai1; Lu, Shaoli1; Yu, Yu1; Wang, Haiying1; McNutt, Michael A.2; Hu, Ye-Guang3; Chen, Yingqi1; Yang, Yang1; Wu, Xin4; Otterson, Gregory A.4; Zhu, Wei-Guo1
刊名: PLOS ONE
发表日期: 2008-06-18
DOI: 10.1371/journal.pone.0002445
卷: 3, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
英文摘要:

5-aza-2 ′-deoxycytidine (5-aza-CdR) is used extensively as a demethylating agent and acts in concert with histone deacetylase inhibitors (HDACl) to induce apoptosis or inhibition of cell proliferation in human cancer cells. Whether the action of 5-aza-CdR in this synergistic effect results from demethylation by this agent is not yet clear. In this study we found that inhibition of cell proliferation was not observed when cells with knockdown of DNA methyltransferase 1 (DNMT1), or double knock down of DNMT1-DNMT3A or DNMT1-DNMT3B were treated with HDACl, implying that the demethylating function of 5-aza-CdR may be not involved in this synergistic effect. Further study showed that there was a causal relationship between 5-aza-CdR induced DNA damage and the amount of [(3)H]-5-aza-CdR incorporated in DNA. However, incorporated [(3)H]-5-aza-CdR gradually decreased when cells were incubated in [(3)H]-5-aza-CdR free medium, indicating that 5-aza-CdR, which is an abnormal base, may be excluded by the cell repair system. It was of interest that HDACl significantly postponed the removal of the incorporated [(3)H]-5-aza-CdR from DNA. Moreover, HDAC inhibitor showed selective synergy with nucleoside analog-induced DNA damage to inhibit cell proliferation, but showed no such effect with other DNA damage stresses such as gamma-ray and UV, etoposide or cisplatin. This study demonstrates that HDACl synergistically inhibits cell proliferation with nucleoside analogs by suppressing removal of incorporated harmful nucleotide analogs from DNA.

语种: 英语
所属项目编号: 30425017 ; 30670417 ; 30621002 ; 2005CB522403 ; 2006AA02Z101 ; 2006CB910300 ; B07001
项目资助者: National Natural Science Foundation of China ; Ministry of Science and Technology of China
WOS记录号: WOS:000263280700030
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51895
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China
3.Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China
4.Ohio State Univ, Comprehensive Canc Ctr, Dept Internal Med, Div Hematol Oncol, Columbus, OH USA

Recommended Citation:
Chai, Guolin,Li, Lian,Zhou, Wen,et al. HDAC Inhibitors Act with 5-aza-2 ′-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells[J]. PLOS ONE,2008,3(6).
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