Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration

doi:10.1038/aps.2016.139

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 天然药物化学研究室

	Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration
	Sun, Jing-ya 2,3; Wang, Ji-dong 1; Wang, Xin2,3 ; Liu, Hong-chun2,3 ; Zhang, Min-min2,3 ; Liu, Yu-chih 5; Zhang, Chen-hua 5; Su, Yi 2,3; Shen, Yan-yan 2,3; Guo, Yue-wei3,4
刊名	ACTA PHARMACOLOGICA SINICA
	2017-04
卷号	38 期号:4 页码:551-560
关键词	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
文献子类	Article
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[81673472] ; National Natural Science Foundation of China[81402966] ; National Natural Science Foundation of China[81520108028] ; National Program on Key Basic Research Project of China[2012CB910704] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020105] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development[00000000]
WOS关键词	HISTONE DEACETYLASE INHIBITORS ; ANDROGEN DEPRIVATION THERAPY ; ROMIDEPSIN ; VORINOSTAT ; EXPRESSION ; RESISTANCE ; TRIAL ; DEPSIPEPTIDE ; MITOXANTRONE ; ABIRATERONE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5953664
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000399192700010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272726]
专题	天然药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药理学第一研究室分子影像中心（筹）
通讯作者	Guo, Yue-wei; Shen, Ai-jun; Geng, Mei-yu
作者单位	1.Zhejiang Hisun Pharmaceut Co Ltd, Taizhou 318000, Peoples R China; 2.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 5.Shanghai ChemPartner Co Ltd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Sun, Jing-ya,Wang, Ji-dong,Wang, Xin,et al. Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration[J]. ACTA PHARMACOLOGICA SINICA,2017,38(4):551-560.
APA	Sun, Jing-ya.,Wang, Ji-dong.,Wang, Xin.,Liu, Hong-chun.,Zhang, Min-min.,...&Geng, Mei-yu.(2017).Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration.ACTA PHARMACOLOGICA SINICA,38(4),551-560.
MLA	Sun, Jing-ya,et al."Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration".ACTA PHARMACOLOGICA SINICA 38.4(2017):551-560.