marinederivedchromopeptideaanovelclassihdacinhibitorsuppresseshumanprostatecancercellproliferationandmigration
文献类型：期刊论文
| 作者 | Sun Jingya1; Wang Jidong2; Wang Xin1 ; Liu Hongchun1; Zhang Minmin1; Liu Yuchih3; Zhang Chenhua3; Su Yi1; Shen Yanyan1; Guo Yuewei4
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| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2017 |
| 卷号 | 38期号:4页码:551 |
| 关键词 | HISTONE DEACETYLASE INHIBITORS ANDROGEN DEPRIVATION THERAPY ROMIDEPSIN VORINOSTAT EXPRESSION RESISTANCE TRIAL DEPSIPEPTIDE MITOXANTRONE ABIRATERONE HDAC chromopeptide A FK228 human prostate cancer cell cycle arrest apoptosis cancer cell migration PC3 xenograft model |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2016.139 |
| 英文摘要 | Histone deacetylases (HDACs), especially HDAC1, 2, 3 and 4, are abundantly expressed and over-activated in prostate cancer that is correlated with the poor prognosis. Thus, inhibition of HDAC activity has emerged as a potential alternative option for prostate cancer therapy. Chromopeptide A is a depsipeptide isolated from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94; it has a chemical structure highly similar to FK228, a class I HDAC inhibitor that is approved by FDA for treating T-cell lymphoma. In this study, we determined whether chromopeptide A, like FK228, acted as a class I HDAC inhibitor, and whether chromopeptide A could inhibit the growth and migration of human prostate cancer in vitro and in vivo. HDAC enzyme selectivity and kinetic analysis revealed that chromopeptide A selectively inhibited the enzymatic activities of HDAC1, 2, 3 and 8 in a substrate non-competitive manner with comparable IC50 values for each HDAC member as FK228 in vitro. Importantly, chromopeptide A dose-dependently suppressed the proliferation of human prostate cancer cell lines PC3, DU145 and LNCaP with IC50 values of 2.43 +/- 0.02, 2.08 +/- 0.16, and 1.75 +/- 0.06 nmol/L, respectively, accompanied by dose-dependent inhibition of HDAC enzymatic activity in PC3 and DU145 cells. Chromopeptide A (0.2-50 nmol/L) caused G(2)/M phase arrest and induced apoptosis in the prostate cancer cell lines. Moreover, chromopeptide A dose-dependently inhibited the migration of PC3 cells. In mice bearing PC3 prostate cancer xenografts, intravenous injection of chromopeptide A (1.6, 3.2 mg/kg, once a week for 18 d) significantly suppressed the tumor growth, which was associated with increased expression levels of Ac-H3 and p21 in tumor tissues. Our results identify chromopeptide A as a novel class I HDAC inhibitor and provide therapeutic strategies that may be implemented in prostate cancer. |
| 资助项目 | [National Natural Science Foundation of China] ; [National Program on Key Basic Research Project of China] ; [Strategic Priority Research Program of the Chinese Academy of Sciences] ; [Personalized Medicines-Molecular Signature-Based Drug Discovery and Development] |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/285712]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海药物研究所 2.Zhejiang Hisun Pharmaceutical Company Ltd 3.Shanghai ChemPartner Co, Ltd 4.中国科学院大学 |
| 推荐引用方式 GB/T 7714 | Sun Jingya,Wang Jidong,Wang Xin,et al. marinederivedchromopeptideaanovelclassihdacinhibitorsuppresseshumanprostatecancercellproliferationandmigration[J]. actapharmacologicasinica,2017,38(4):551. |
| APA | Sun Jingya.,Wang Jidong.,Wang Xin.,Liu Hongchun.,Zhang Minmin.,...&Geng Meiyu.(2017).marinederivedchromopeptideaanovelclassihdacinhibitorsuppresseshumanprostatecancercellproliferationandmigration.actapharmacologicasinica,38(4),551. |
| MLA | Sun Jingya,et al."marinederivedchromopeptideaanovelclassihdacinhibitorsuppresseshumanprostatecancercellproliferationandmigration".actapharmacologicasinica 38.4(2017):551. |
入库方式： OAI收割
来源：上海药物研究所
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