Tanshinone IIA triggers p53 responses and apoptosis by RNA polymerase II upon DNA minor groove binding
发表时间：2019-03-09
点击次数：
- 论文类型：
- 期刊论文
- 第一作者：
- Zhang, Zhichao
- 通讯作者：
- Zhang, ZC (reprint author), 158-89 Zhongshan Rd, Dalian 116012, Peoples R China.
- 合写作者：
- Gao, Jin,Wang, Yuanyuan,Song, Ting,Zhang, Jing,Wu, Guiye,Zhang, Tiantai,Du, Guanhua
- 发表时间：
- 2009-11-15
- 发表刊物：
- BIOCHEMICAL PHARMACOLOGY
- 收录刊物：
- SCIE、PubMed、Scopus
- 文献类型：
- J
- 卷号：
- 78
- 期号：
- 10
- 页面范围：
- 1316-1322
- ISSN号：
- 0006-2952
- 关键字：
- Tanshinone IIA; DNA minor groove binder; RNA polymerase II; Apoptosis
- 摘要：
- Our previous work has shown that tainshinone IIA (Tan IIA) is a DNA minor groove binder instead of an intercalator as previously thought. In this study, we have further demonstrated that the molecular antitumor pharmacology of Tan IIA is dependent on its groove-binding capability. First,we investigated the structure damage to duplex DNA upon Tan IIA binding using circular dichroism spectra. Subsequently, we performed western blot, flow cytometry analysis, chromatin immunoprecipitation, and quantitative real-time PCR to illustrate the RNAPII degradation, phosphorylation, and distribution along the transcribed gene in H22 cells exposed to Tan IIA. In addition, p53 activation and apoptosis induction in both cultured H22 cells and in mice bearing the ascitic-type H22 were measured following Tan IIA treatment. It was revealed that Tan IIA decreases the level of RNAPII by altering DNA structure. At the low dose range (0.2-4 mu M) of Tan IIA exposure, the DNA structure damage results in the inhibition of RNAPH binding to DNA and the initiation of RNAPII phosphorylation, while higher concentrations of Tan IIA (4-20 mu M) cause complete phosphorylation and degradation of RNAPII followed by p53 activation and apoptosis. A similar apoptosis induction by RNAPII was observed in animals. Apoptosis of tumor cells from ascitic fluid was not detected until RNAPII levels were downregulated by Tan IIA, which requires 40 mg/kg body weight of Tan IIA It was concluded that DNA-conformational-damage-dependent RNAPII response upon groove binding is the molecular basis of the antitumor property of Tan IIA, in vivo and in vitro. (C) 2009 Elsevier Inc. All rights reserved.
- 是否译文：
- 否
- 上一条：3-Thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) Based Molecules as Potent, Dual Inhibitors of B-Cell Lymphoma 2 (Bcl-2) and Myeloid Cell Leukemia Sequence 1 (Mcl-1): Structure-Based Design and Structure-Activity Relationship
- 下一条：Tanshinone IIA Interacts with DNA by Minor Groove-Binding
