Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells
Li Dong1,2; Song Xiao-Yi1,3; Yue Qing-Xi1,3; Cui Ya-Jun3; Liu Miao1; Feng Li-Xing1; Wu Wan-Ying1; Jiang Bao-Hong1; Yang Min1; Qu Xiao-Bo2
刊名CHINESE JOURNAL OF NATURAL MEDICINES
2015-01
卷号13期号:1页码:41-51
关键词Gambogic acid MDA-MB-231 cells Anti-cancer Proteomic Bioinformatic
ISSN号2095-6975
文献子类Article
英文摘要Gambogic acid (GA) is an anticancer agent in phase IIb clinical trial in China but its mechanism of action has not been fully clarified. The present study was designed to search the possible target-related proteins of GA in cancer cells using proteomic method and establish possible network using bioinformatic analysis. Cytotoxicity and anti-migration effects of GA in MDA-MB-231 cells were checked using MTT assay, flow cytometry, wound migration assay, and chamber migration assay. Possible target-related proteins of GA at early (3 h) and late stage (24 h) of treatment were searched using a proteomic technology, two-dimensional electrophoresis (2-DE). The possible network of GA was established using bioinformatic analysis. The intracellular expression levels of vimentin, keratin 18, and calumenin were determined using Western blotting. GA inhibited cell proliferation and induced cell cycle arrest at G2/M phase and apoptosis in MDA-MB-231 cells. Additionally, GA exhibited anti-migration effects at non-toxic doses. In 2-DE analysis, totally 23 possible GA targeted proteins were found, including those with functions in cytoskeleton and transport, regulation of redox state, metabolism, ubiquitin-proteasome system, transcription and translation, protein transport and modification, and cytokine. Network analysis of these proteins suggested that cytoskeleton-related proteins might play important roles in the effects of GA. Results of Western blotting confirmed the cleavage of vimentin, increase in keratin 18, and decrease in calumenin levels in GA-treated cells. In summary, GA is a multi-target compound and its anti-cancer effects may be based on several target-related proteins such as cytoskeleton-related proteins.
资助项目Twelfth Five-Year National Science & Technology Support Program[2012BAI 29B06] ; Shanghai Science & Technology Support Program[13431900 401] ; China Postdoctoral Science Foundation Funded Project[2012M5 10907] ; Shanghai Postdoctoral Scientific Program[13R21417800] ; Sanofi-Aventis-Shanghai Institutes for Biological Sciences Scholarship Program, the National Nature Science Foundation[81302809] ; Sanofi-Aventis-Shanghai Institutes for Biological Sciences Scholarship Program, the National Nature Science Foundation[81373964] ; Postdoctor Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2012KIP516]
WOS关键词INDUCED APOPTOSIS ; INHIBITS ANGIOGENESIS ; UP-REGULATION ; CYCLE ARREST ; CANCER-CELLS ; PHOSPHORYLATION ; ACCUMULATION ; DEGRADATION ; RESISTANCE ; MECHANISM
WOS研究方向Integrative & Complementary Medicine ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5345281
出版者CHINESE JOURNAL NATURAL MEDICINES
WOS记录号WOS:000349475400005
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/276756]  
专题上海中药现代化研究中心
通讯作者Liu Xuan
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Changchun Univ Chinese Med, Changchun 130117, Peoples R China;
3.Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China
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Li Dong,Song Xiao-Yi,Yue Qing-Xi,et al. Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells[J]. CHINESE JOURNAL OF NATURAL MEDICINES,2015,13(1):41-51.
APA Li Dong.,Song Xiao-Yi.,Yue Qing-Xi.,Cui Ya-Jun.,Liu Miao.,...&Guo De-An.(2015).Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells.CHINESE JOURNAL OF NATURAL MEDICINES,13(1),41-51.
MLA Li Dong,et al."Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells".CHINESE JOURNAL OF NATURAL MEDICINES 13.1(2015):41-51.
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