Cu2+ is required for pyrrolidine dithiocarbamate to inhibit histone acetylation and induce human leukemia cell apoptosis
文献类型：期刊论文
| 作者 | Chen, J; Du, CS; Kang, JH; Wang, JM |
| 刊名 | CHEMICO-BIOLOGICAL INTERACTIONS
 |
| 出版日期 | 2008 |
| 卷号 | 171期号:1页码:26-36 |
| 关键词 | copper pyrrolidine dithiocarbamate histone acetylation histone acetyltransferase histone deacetylase apoptosis |
| 通讯作者 | Wang, JM (reprint author), Second Military Med Univ, Changhai Hosp, Dept Hematol, Shanghai 200433, Peoples R China.,jhkang@sibs.ac.cn |
| 英文摘要 | Pyrrolidine dithiocarbamate (PDTC) has been considered as a potential anticancer drug due to its powerful apoptogenic effect towards cancer cells, where Cu2+ plays a distinct yet undefined role. Here we report that Cu2+ is critically needed for PDTC to inhibit histone acetylation in both human leukemia HL-60 cells and human hepatoma Hep3B cells. The inhibition of histone acetylation mainly resulted from the increase of intracellular Cu2+, but was not due to the inhibition of NF-kappa B activity by PDTC-Cu2+ since the combinations of Cu2+ with SN50, MG132 (two known NF-kappa B inhibitors), or bathocuproine disulfonate (BCS, a specific Cu2+ chelator that does not cross the plasma membrane), did not lead to obvious inhibition of histone acetylation. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are the enzymes controlling the state of histone acetylation in vivo. Cells exposed to PDTC-Cu2+ showed a comparable decrease in histone acetylation levels in HL-60 cells in the absence or presence of the HDAC inhibitors, trichostatin A (TSA) or sodium butyrate (NaBu); the inhibition rates were about 45, 44 and 43%, respectively. PDTC-Cu2+ had no effect on the activity of HDAC in vitro, but significantly inhibited the HAT activity both in HL-60 cells and in a cell-free in vitro system. PDTC-Cu2+ also induced HL-60 cell apoptosis, and treating cells with TSA, NaBu or BCS significantly attenuated the apoptosis induced by PDTC-Cu2+. Collectively, these results showed that inhibition of histone acetylation represents a distinct mechanism for the cytotoxicity of PDTC in the presence of Cu2+, where HAT is its possible molecular target. (c) 2007 Elsevier Ireland Ltd. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology |
| 关键词[WOS] | NF-KAPPA-B ; DEACETYLASE INHIBITORS ; COLORECTAL-CANCER ; REDOX CYCLE ; COPPER ; ACTIVATION ; HYPOACETYLATION ; LEVEL ; DEATH ; PROLIFERATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000252504500003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1320]  |
| 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 | Chen, J,Du, CS,Kang, JH,et al. Cu2+ is required for pyrrolidine dithiocarbamate to inhibit histone acetylation and induce human leukemia cell apoptosis[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2008,171(1):26-36. |
| APA | Chen, J,Du, CS,Kang, JH,&Wang, JM.(2008).Cu2+ is required for pyrrolidine dithiocarbamate to inhibit histone acetylation and induce human leukemia cell apoptosis.CHEMICO-BIOLOGICAL INTERACTIONS,171(1),26-36. |
| MLA | Chen, J,et al."Cu2+ is required for pyrrolidine dithiocarbamate to inhibit histone acetylation and induce human leukemia cell apoptosis".CHEMICO-BIOLOGICAL INTERACTIONS 171.1(2008):26-36. |
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。