Comparative proteomics-network analysis of proteins responsible for ursolic acid-induced cytotoxicity in colorectal cancer cells

被引:7
作者
Cai, Qiaoyan [1 ,2 ]
Lin, Jing [1 ,2 ]
Zhang, Ling [1 ,2 ]
Lin, Jiumao [1 ,2 ]
Wang, Lili [1 ,2 ]
Chen, Daxin [1 ,2 ]
Peng, Jun [1 ,2 ]
机构
[1] Fujian Univ Tradit Chinese Med, Acad Integrat Med, 1 Qiuyang Rd, Fuzhou 350122, Fujian, Peoples R China
[2] Fujian Univ Tradit Chinese Med, Fujian Key Lab Integrat Med Geriatr, Fuzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Proteomics; ursolic acid; colorectal cancer; apoptosis; cytotoxicity; MULTIPLE SIGNALING PATHWAYS; HEPATOCELLULAR-CARCINOMA; INDUCED APOPTOSIS; LUNG-CANCER; ADENOCARCINOMA; SURVIVAL; HSP27; P53; HEAT-SHOCK-PROTEIN-70; PROLIFERATION;
D O I
10.1177/1010428317695015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ursolic acid is a key active compound present in many medicinal herbs that have been widely used in traditional Chinese medicine for the clinical treatment of various cancers. However, the precise mechanisms of its antitumor activity have been poorly understood. To identify the cellular targets of ursolic acid, two-dimensional gel electrophoresis combined with mass spectrometry was performed in this study, which identified 15 proteins with significantly altered levels in protein expression. This demonstrated that ursolic acid-induced cytotoxicity in colorectal cancer cells involves dysregulation in protein folding, signal transduction, cell proliferation, cell cycle, and apoptosis. Corresponding protein regulation was also confirmed by Western blotting. Furthermore, the study of functional association between these 15 proteins revealed that 10 were closely related in a protein-protein interaction network, whereby the proteins either had a direct interaction with each other or were associated via only one intermediary protein. In this instance, the ATP5B/CALR/HSP90B1/HSPB1/HSPD1-signaling network was revealed as the predominant target which was associated with the majority of the observed protein-protein interactions. As a result, the identified targets may be useful in explaining the anticancer mechanisms of ursolic acid and as potential targets for colorectal cancer therapy.
引用
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页数:10
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共 38 条
[1]  
Andersson D, 2003, ANTICANCER RES, V23, P3317
[2]   HspB1, HspB5 and HspB4 in Human Cancers: Potent Oncogenic Role of Some of Their Client Proteins [J].
Arrigo, Andre-Patrick ;
Gibert, Benjamin .
CANCERS, 2014, 6 (01) :333-365
[3]   Two-dimensional gel analysis of human endometrial proteins: characterization of proteins with increased expression in hyperplasia and adenocarcinoma [J].
Byrjalsen, I ;
Larsen, PM ;
Fey, SJ ;
Nilas, L ;
Larsen, MR ;
Christiansen, C .
MOLECULAR HUMAN REPRODUCTION, 1999, 5 (08) :748-756
[4]   HSP60 and HSP10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease [J].
Cappello, Francesco ;
Di Stefano, Antonino ;
David, Sabrina ;
Rappa, Francesco ;
Anzalone, Rita ;
La Rocca, Giampiero ;
D'Anna, Siivestro E. ;
Magno, Francesca ;
Donner, Claudio F. ;
Balbi, Bruno ;
Zummo, Giovanni .
CANCER, 2006, 107 (10) :2417-2424
[5]   Effects of ursolic acid on different steps of the angiogenic process [J].
Cárdenas, C ;
Quesada, AR ;
Medina, MA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 320 (02) :402-408
[6]   Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival [J].
Cawthorn, Thomas R. ;
Moreno, Juan C. ;
Dharsee, Moyez ;
Danh Tran-Thanh ;
Ackloo, Suzanne ;
Zhu, Pei Hong ;
Sardana, Girish ;
Chen, Jian ;
Kupchak, Peter ;
Jacks, Lindsay M. ;
Miller, Naomi A. ;
Youngson, Bruce J. ;
Iakovlev, Vladimir ;
Guidos, Cynthia J. ;
Vallis, Katherine A. ;
Evans, Kenneth R. ;
McCready, David ;
Leong, Wey L. ;
Done, Susan J. .
PLOS ONE, 2012, 7 (02)
[7]   Cyclic adenosine monophosphate inhibits ursolic acid-induced apoptosis via activation of protein kinase A in human leukaemic HL-60 cells [J].
Choi, BM ;
Park, R ;
Pae, HO ;
Yoo, JC ;
Kim, YC ;
Jun, CD ;
Jung, BH ;
Oh, GS ;
So, HS ;
Kim, YM ;
Chung, HT .
PHARMACOLOGY & TOXICOLOGY, 2000, 86 (02) :53-58
[8]   Effects of heat stress on the level of heat shock protein 70 on the surface of hepatocellular carcinoma Hep G2 cells: implications for the treatment of tumors [J].
Cui, Naizhong ;
Xu, Yongping ;
Cao, Zhenhui ;
Xu, Fanxing ;
Zhang, Peng ;
Jin, Liji .
TUMOR BIOLOGY, 2013, 34 (02) :743-748
[9]   Mortalin is over-expressed by colorectal adenocarcinomas and correlates with poor survival [J].
Dundas, SR ;
Lawrie, LC ;
Rooney, PH ;
Murray, GI .
JOURNAL OF PATHOLOGY, 2005, 205 (01) :74-81
[10]   Inhibitory effect of ursolic acid on B16 proliferation through cell cycle arrest [J].
Essaady, D ;
Simon, A ;
Ollier, M ;
Maurizis, JC ;
Chulia, AJ ;
Delage, C .
CANCER LETTERS, 1996, 106 (02) :193-197