An Oxygen-Chelate Complex, Palladium Bis-acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather than Interacting with DNA

doi:10.1021/jm4016312

科研成果详情

题名	An Oxygen-Chelate Complex, Palladium Bis-acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather than Interacting with DNA
作者	Wang, Yi; Hu, Jie; Cai, Yuepiao; Xu, Shanmei; Weng, Bixia; Peng, Kesong; Wei, Xiaoyan; Wei, Tao; Zhou, Huiping; Li, Xiaokun; Liang, Guang
发表日期	2013-12-12
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	DEATH PROGRAM ; CRYSTAL-STRUCTURE ; CANCER-CELLS ; RESISTANCE ; CISPLATIN ; CHOP ; PLATINUM(II) ; METABOLISM ; EXPRESSION ; LIGANDS
摘要	Current precious-metal-containing anticancer agents are mostly chelated with N-containing ligands and function by interacting with DNA. In the present study, Pd(acac)(2), a Pd(II) complex containing four O-donor ligands, has been evaluated as an active anticancer agent. Pd(acac)(2) showed no interaction with N-ligand-containing DNA and the S-ligand-containing DMSO, probably because of the two six-member chelate rings that limit the release of the central Pd nuclei to bind to other ligands. Importantly, we found that Pd(acac)(2) exhibited better growth inhibitory effects than cisplatin in several cancer cells. Treatment with Pd(acac), significantly induced apoptosis in H460 cells. Mechanistically, Pd(acac)(2) induced the activation of a series of key components in ER stress-mediated apoptotic pathway, followed by caspase cleavage and activation, while cisplatin showed no similar effects. CHOP knockdown by specific siRNA significantly attenuated Pd(acac)(2)-induced cell apoptosis. Finally, Pd(acac)(2) significantly inhibits H460 cell growth in xenograft mouse models. Taken together, these mechanistic insights on Pd(acac)(2) provide us with a novel mechanism and strategy for the development of precious-metal-based anticancer drugs.
资助项目	National Natural Science Fundings of China [81102452, 81270489, 81173083]; Zhejiang Provicial Project of Key Scientific Group [2010R50042]; Zhejiang Provincial Natural Science Fundation [LY12H30005, LY12H16003]; Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
出版者	AMER CHEMICAL SOC
出版地	WASHINGTON
ISSN	0022-2623
EISSN	1520-4804
卷号	56 期号:23 页码:9601-9611
DOI	10.1021/jm4016312
页数	11
WOS类目	Chemistry, Medicinal
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000328529700018
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	24274598
SCOPUSEID	2-s2.0-84890513359
自科自定义期刊分类	T3(B)类
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,China
Scopus学科分类	Molecular Medicine;Drug Discovery
TOP期刊	TOP期刊
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/11811
专题	药学院（分析测试中心）
通讯作者	Liang, Guang
作者单位	Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Wang, Yi,Hu, Jie,Cai, Yuepiao,et al. An Oxygen-Chelate Complex, Palladium Bis-acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather than Interacting with DNA[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(23):9601-9611.
APA	Wang, Yi., Hu, Jie., Cai, Yuepiao., Xu, Shanmei., Weng, Bixia., ... & Liang, Guang. (2013). An Oxygen-Chelate Complex, Palladium Bis-acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather than Interacting with DNA. JOURNAL OF MEDICINAL CHEMISTRY, 56(23), 9601-9611.
MLA	Wang, Yi,et al."An Oxygen-Chelate Complex, Palladium Bis-acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather than Interacting with DNA".JOURNAL OF MEDICINAL CHEMISTRY 56.23(2013):9601-9611.