Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid

doi:10.1074/mcp.M115.053272

	Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid
	Yue, Qingxi 2,3,4; Feng, Lixing 2; Cao, Biyin 1; Liu, Miao 2; Zhang, Dongmei 2; Wu, Wanying2 ; Jiang, Baohong2 ; Yang, Min 2; Liu, Xuan 2; Guo, Dean2,4
刊名	MOLECULAR & CELLULAR PROTEOMICS
	2016-01
卷号	15 期号:1 页码:26-44
ISSN号	1535-9476
DOI	10.1074/mcp.M115.053272
文献子类	Article
英文摘要	Gambogic acid (GA) is an anticancer agent in phase IIb clinical trial in China. In HeLa cells, GA inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis, as showed by results of MTT assay and flow cytometric analysis. Possible target-related proteins of GA were searched using comparative proteomic analysis (2-DE) and nine proteins at early (3 h) stage together with nine proteins at late (24 h) stage were found. Vimentin was the only target-related protein found at both early and late stage. Results of both 2-DE analysis and Western blotting assay suggested cleavage of vimentin induced by GA. MS/MS analysis of cleaved vimentin peptides indicated possible cleavage sites of vimentin at or near ser51 and glu425. Results of targeted proteomic analysis showed that GA induced change in phosphorylation state of the vimentin head domain (aa51-64). Caspase inhibitors could not abrogate GA-induced cleavage of vimentin. Over-expression of vimentin ameliorated cytotoxicity of GA in HeLa cells. The GA-activated signal transduction, from p38 MAPK, heat shock protein 27 (HSP27), vimentin, dysfunction of cytoskeleton, to cell death, was predicted and then confirmed. Results of animal study showed that GA treatment inhibited tumor growth in HeLa tumor-bearing mice and cleavage of vimentin could be observed in tumor xenografts of GA-treated animals. Results of immunohistochemical staining also showed down-regulated vimentin level in tumor xenografts of GA-treated animals. Furthermore, compared with cytotoxicity of GA in HeLa cells, cytotoxicity of GA in MCF-7 cells with low level of vimentin was weaker whereas cytotoxicity of GA in MG-63 cells with high level of vimentin was stronger. These results indicated the important role of vimentin in the cyto-toxicity of GA. The effects of GA on vimentin and other epithelial-to-mesenchymal transition (EMT) markers provided suggestion for better usage of GA in clinic.
资助项目	Twelfth Five-Year National Science & Technology Support Program[2012BAI29B06] ; Shanghai Science & Technology Support Program[13431900401] ; China Postdoctoral Science Foundation[2012M510907] ; Shanghai Postdoctoral Scientific Program[13R21417800] ; Postdoctor Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2012KIP516] ; Sanofi-Aventis-Shanghai Institutes for Biological Sciences Scholarship Program[00000000] ; National Nature Science Foundation[81302809] ; National Nature Science Foundation[81373964] ; People's Hospital, School of Medicine, Shanghai Jiaotong University[00000000] ; [syzrc2014-001] ; [syz2014-005]
WOS关键词	INTERMEDIATE-FILAMENTS ; INDUCED APOPTOSIS ; CYCLE ARREST ; SIGNALING PATHWAY ; CANCER-CELLS ; IN-VITRO ; PHOSPHORYLATION ; HSP27 ; EXPRESSION ; PROTEINS
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000367461000003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276270]
专题	中国科学院上海药物研究所
通讯作者	Yue, Qingxi
作者单位	1.Soochow Univ, Coll Pharmaceut Sci, Suzhou, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Inst Oncol, Shanghai 200030, Peoples R China; 4.Shanghai Univ Tradit Chinese Med, Coll Chinese Mat Medica, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Yue, Qingxi,Feng, Lixing,Cao, Biyin,et al. Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid[J]. MOLECULAR & CELLULAR PROTEOMICS,2016,15(1):26-44.
APA	Yue, Qingxi.,Feng, Lixing.,Cao, Biyin.,Liu, Miao.,Zhang, Dongmei.,...&Guo, Dean.(2016).Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid.MOLECULAR & CELLULAR PROTEOMICS,15(1),26-44.
MLA	Yue, Qingxi,et al."Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid".MOLECULAR & CELLULAR PROTEOMICS 15.1(2016):26-44.