HDAC Inhibitors Act with 5-aza-2 '-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells
文献类型：期刊论文
| 作者 | Chai, GL; Li, L; Zhou, W; Wu, LP; Zhao, Y; Wang, DL; Lu, SL; Yu, Y; Wang, HY; McNutt, MA |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2008 |
| 卷号 | 3期号:6页码:e2445-e2445 |
| 通讯作者 | Chai, GL (reprint author), Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.,zhuweiguo@bjmu.edu.cn |
| 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. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000263280700030 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1385]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Chai, GL,Li, L,Zhou, W,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):e2445-e2445. |
| APA | Chai, GL.,Li, L.,Zhou, W.,Wu, LP.,Zhao, Y.,...&Zhu, WG.(2008).HDAC Inhibitors Act with 5-aza-2 '-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells.PLOS ONE,3(6),e2445-e2445. |
| MLA | Chai, GL,et al."HDAC Inhibitors Act with 5-aza-2 '-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells".PLOS ONE 3.6(2008):e2445-e2445. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。