Mitochondria-targeted platinum(II) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of beta-catenin

doi:10.1039/c6mt00188b

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	Mitochondria-targeted platinum(II) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of beta-catenin
	Li, JL; He, XL; Zou, YL; Chen, DD; Yang, LC; Rao, JM; Chen, HB; Chan, MCW; Li, L; Guo, ZQ; Zhang, LSW; Chen, CY; Chen CY(陈春英)
	2017
发表期刊	METALLOMICS (IF:3.975[JCR-2016],3.847[5-Year])
ISSN	1756-5901
EISSN	1756-591X
卷号	9 期号:6 页码:726-733
文章类型	Article
摘要	Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(II) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis. Interestingly, PIP-platin can promote cell adhesion within several hours and the cells became hard to dislodge from the culture plate. A wound healing assay, transwell migration/invasion assay and 3D spheroid migration assay all demonstrated that PIP-platin can inhibit cell migration/invasion. To illustrate the associated mechanisms, we investigated the intracellular trafficking of beta-catenin, a central protein in the regulation of cell adhesion, and gene transcription for cell proliferation. Upon treatment with PIP-platin, this protein can translocate onto the plasma membrane for increased cell adhesion. In addition, PIP-platin was demonstrated to efficiently inhibit Wnt signaling by blocking the translocation of beta-catenin into the nuclei, thereby preventing cell proliferation. We demonstrate that, accordingly, PIP-platin has remarkable potential for intracellular delivery in mitochondria and has inhibitory effects on cancer cell proliferation and migration/invasion through beta-catenin, and may therefore be exploited as a dual-functional antitumor drug candidate in cancer treatment.
DOI	10.1039/c6mt00188b
关键词[WOS]	CANCER-CELLS ; CYTOCHROME-C ; CISPLATIN ; APOPTOSIS ; DELIVERY ; AGENTS ; DNA ; CYTOTOXICITY ; PRODRUGS ; THERAPY
收录类别	SCI ; EI ; SCOPUS
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000403968800012
EI入藏号	20172703889057
EI主题词	Assays - Cell adhesion - Cell culture - Cell membranes - Cell proliferation - Controlled drug delivery - Diseases - Mitochondria - Platinum compounds - Proteins - Targeted drug delivery - Transcription - Tumors
EI分类号	461 Bioengineering and Biology - 801 Chemistry - 804.1 Organic Compounds
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://ir.ihep.ac.cn/handle/311005/285162
专题	多学科研究中心
作者单位	中国科学院高能物理研究所
第一作者单位	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Li, JL,He, XL,Zou, YL,et al. Mitochondria-targeted platinum(II) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of beta-catenin[J]. METALLOMICS,2017,9(6):726-733.
APA	Li, JL.,He, XL.,Zou, YL.,Chen, DD.,Yang, LC.,...&陈春英.(2017).Mitochondria-targeted platinum(II) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of beta-catenin.METALLOMICS,9(6),726-733.
MLA	Li, JL,et al."Mitochondria-targeted platinum(II) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of beta-catenin".METALLOMICS 9.6(2017):726-733.

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