Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells

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	Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells
	Jia, JL(贾俊丽); Fei, H(费浩)
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2013-05-09
卷号	56 期号:9 页码:3636-3644
通讯作者	Zhou, M(周明)
英文摘要	The cellular behavior and toxicity effect of organometallic complexes depend largely on their peripheral ligands. In this study, we have synthesized a series of novel luminescent cationic iridium(III) complexes by tuning the ancillary N boolean AND N ligand based on a structure [Ir(ppy)(2)((NN)-N-boolean AND)](+) (ppy = 1-phenyl-pyridine; (NN)-N-boolean AND = 2,2'-bipyridine (bpy, 1) or phenanthroline (phen, 2) or 4,7-diphenyl-1,10- phenanthroline (DIP, 3)). As the size of coordinated (NN)-N-boolean AND ligand increases, absorbance/emission efficiency, quantum yields, lipophilicity, and cell uptake rates of the complexes also increase, in a general order: 3 > 2 > 1. All three complexes display anticancer activity, with 3 exhibiting the highest cellular uptake efficiency and the greatest cytotoxic activities in several cancer cell lines with IC(50)s lower than that of cisplatin. Because of its strong hydrophobic nature, the death inducer 3 was found to accumulate favorably to endoplasmic reticulum (ER) and to cause ER stress in cells. The fast cytosolic release of calcium from stressed ER disturbed the morphology and function of mitochondria, initiating an intrinsic apoptotic pathway. Understanding of the cell death mechanism would help further structure-activity optimization on these novel Ir(III) complexes as emerging cancer therapeutics.
收录类别	SCI
语种	英语
WOS记录号	WOS:000318892500018
公开日期	2014-01-15
内容类型	期刊论文
源URL	[http://ir.sinano.ac.cn/handle/332007/1358]
专题	苏州纳米技术与纳米仿生研究所_纳米生物医学与安全研究部_离职团队苏州纳米技术与纳米仿生研究所_纳米生物医学与安全研究部_费浩团队
推荐引用方式 GB/T 7714	Jia, JL,Fei, H. Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(9):3636-3644.
APA	Jia, JL,&Fei, H.(2013).Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells.JOURNAL OF MEDICINAL CHEMISTRY,56(9),3636-3644.
MLA	Jia, JL,et al."Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells".JOURNAL OF MEDICINAL CHEMISTRY 56.9(2013):3636-3644.