5-Aza-2′-deoxycytidine reactivates expression of RUNX3 by deletion of DNA methyltransferases leading to caspase independent apoptosis in colorectal cancer Lovo cells
5-Aza-2′-deoxycytidine reactivates expression of RUNX3 by deletion of DNA methyltransferases leading to caspase independent apoptosis in colorectal cancer Lovo cells
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DOI：
10.1016/j.biopha.2008.08.013
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发表时间：
2009-08-01
影响因子：
7.5
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Deng, Tao;Zhang, Yan
DNA甲基化抑制剂5-Aza-2'-脱氧胞苷（5-Aza-CdR）在治疗癌症方面具有治疗价值。然而，5-Aza-CdR诱导抗肿瘤活性的机制是一个尚未解决的重要问题。在本研究中，我们发现，在有限浓度下，5-Aza-CdR可以抑制结直肠癌Lovo细胞的增殖，并增加DNA损伤引起的细胞凋亡，这种凋亡不依赖于caspase途径。关于其机制，我们首次研究了通过下调DNA甲基转移酶3a、DNMT3b，然后重新激活RUNX3的表达来调节Lovo细胞的细胞毒性。因此，我们得出结论，RUNX3是5-Aza-CdR对结直肠癌Lovo细胞甲基转移酶依赖作用的相关靶点。(C) 2008 Elsevier Masson SAS。版权所有。
The DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) has therapeutic value for the treatment of cancer. However, the mechanism by which 5-Aza-CdR induces antineoplastic activity is an important unresolved question. In this study, we found that 5-Aza-CdR at limited concentrations induced inhibition of colorectal cancer Lovo cell proliferation as well as increased apoptosis caused by DNA damage, which was independent of the caspase pathway. Regarding the mechanisms, for the first time, we examined that cytotoxicity against Lovo cells was regulated via down-regulation of DNA methyltransferase 3a, DNMT3b and then reactivated the expression of RUNX3. We therefore conclude that RUNX3 is a relevant target for methyltransferases dependent effects of 5-Aza-CdR on colorectal cancer Lovo cells. (C) 2008 Elsevier Masson SAS. All rights reserved.