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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, Jingling1,2; He, Xiaoli3; Zou, Yeling2,4,5; Chen, Dandan1,2; Yang, Liecheng1,2; Rao, Jiaming1,2; Chen, Huabing4,5; Chan, Michael C. W.6; Li, Lin3; Guo, Zhengqing1,2
刊名	Metallomics
	2017-06-01
卷号	9期号:6页码:726-733
ISSN号	1756-5901
DOI	10.1039/c6mt00188b
通讯作者	Guo, zhengqing(zqguo@suda.edu.cn) ; Zhang, leshuai w.(zhangls@suda.edu.cn)
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.
WOS关键词	CANCER-CELLS ; CYTOCHROME-C ; CISPLATIN ; APOPTOSIS ; DELIVERY ; AGENTS ; DNA ; CYTOTOXICITY ; PRODRUGS ; THERAPY
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000403968800012
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2177309
专题	高能物理研究所
通讯作者	Guo, Zhengqing; Zhang, Leshuai W.
作者单位	1.Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Peoples R China 2.Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher, Suzhou 215123, Peoples R China 3.Chinese Acad Sci, Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 4.Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215123, Peoples R China 5.Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China 6.City Univ Hong Kong, Dept Biol & Chem, Tat Chee Ave, Kowloon, Hong Kong, Peoples R China 7.Chinese Acad Sci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China 8.Chinese Acad Sci, Inst High Energy Phys, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Li, Jingling,He, Xiaoli,Zou, Yeling,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, Jingling.,He, Xiaoli.,Zou, Yeling.,Chen, Dandan.,Yang, Liecheng.,...&Chen, Chunying.(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, Jingling,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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