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

	Mitochondria-targeted platinum(II) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of beta-catenin
	Li, L; Guo, ZQ; Zhang, LSW; Chen CY(陈春英); Chen, CY; Li, JL; He, XL; Zou, YL; Chen, DD; Yang, LC
刊名	METALLOMICS
	2017
卷号	9 期号:6 页码:726-733
ISSN号	1756-5901
DOI	10.1039/c6mt00188b
文献子类	Article
英文摘要	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.
电子版国际标准刊号	1756-591X
WOS关键词	CANCER-CELLS ; CYTOCHROME-C ; CISPLATIN ; APOPTOSIS ; DELIVERY ; AGENTS ; DNA ; CYTOTOXICITY ; PRODRUGS ; THERAPY
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
WOS记录号	WOS:000403968800012
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/285162]
专题	高能物理研究所_多学科研究中心
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, L,Guo, ZQ,Zhang, LSW,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, L.,Guo, ZQ.,Zhang, LSW.,陈春英.,Chen, CY.,...&Chan, MCW.(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, L,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.