PXD002975

PXD002975 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis revealed the important role of vimentin in human cervical carcinoma HeLa cells treated with gambogic acid
Description	Gambogic acid (GA) is an anti-cancer 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 9 proteins at early (3 h) stage together with 9 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 aa51 and aa425. 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 while cytotoxicity of GA in MG-63 cells with high level of vimentin was stronger. These results indicated the important role of vimentin in the cytotoxicity 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.
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_07:56:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	zhang yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	4700 Proteomics Analyzer

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-25 06:27:51	ID requested
⏵ 1	2018-10-24 07:56:55	announced

Yue Q, Feng L, Cao B, Liu M, Zhang D, Wu W, Jiang B, Yang M, Liu X, Guo D, Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid. Mol Cell Proteomics, 15(1):26-44(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: gambogic acid, anti-cancer, proteomics, vimentin

De-An Guo
contact affiliation	Shanghai Institute of Materia Medica, Chinese Academy of Sciences
contact email	daguo@simm.ac.cn
lab head
zhang yang
contact affiliation	fudan
contact email	zhangyang@fudan.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/10/PXD002975

PRIDE project URI

• PRIDE
  1. PXD002975
     1. Label: PRIDE project
     2. Name: Proteomic analysis revealed the important role of vimentin in human cervical carcinoma HeLa cells treated with gambogic acid