Proteomic identification of molecular targets of gambogic acid: Role of stathmin in hepatocellular carcinoma
Gamboge has been developed as an injectable drug for cancer treatment in China. In this study, the inhibition ratio and their IC₅₀ values of two derivatives from Gamboge in hepatocellular carcinoma (HCC) were determined. Proteomic approach was employed to reveal the target proteins of these two deri...
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Published in | Proteomics (Weinheim) Vol. 9; no. 2; pp. 242 - 253 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Weinheim
Wiley-VCH Verlag
01.01.2009
WILEY-VCH Verlag WILEY‐VCH Verlag Wiley-VCH |
Subjects | |
Online Access | Get full text |
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Summary: | Gamboge has been developed as an injectable drug for cancer treatment in China. In this study, the inhibition ratio and their IC₅₀ values of two derivatives from Gamboge in hepatocellular carcinoma (HCC) were determined. Proteomic approach was employed to reveal the target proteins of these two derivatives, gambogic acid (GA), and gambogenic acid (GEA). HCC cells were cultured under varied conditions with the addition of either GA or GEA. Twenty differentially expressed proteins were identified and the four most distinctly expressed proteins were further validated by Western blotting. GA and GEA revealed inhibitory effects on HCC cell proliferation. The expression of cyclin-dependent kinase 4 inhibitor A and guanine nucleotide-binding protein β subunit 1 were upregulated by both xanthones, whilst the expression of 14-3-3 protein sigma and stathmin 1 (STMN1) were downregulated. Furthermore, overexpression of STMN1 in HCC cells decreased their sensitivity, whilst small interfering RNAs targeting STMN1 enhanced their sensitivity to GA and GEA. In conclusion, our study suggested for the first time that STMN1 might be a major target for GA and GEA in combating HCC. Further investigation may lead to a new generation of anticancer drugs exerting synergistic effect with conventional therapy, thus to promote treatment efficacy. |
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Bibliography: | http://dx.doi.org/10.1002/pmic.200800155 Foundation of Guangzhou Science and Technology Bureau - No. 2005Z1-E0131 The Chinese University of Hong Kong - No. 204127; No. 2041345 istex:0D26D3BA20283FCB50C6908C8DB96BBDB1B78F81 Li Ka Shing Institute of Health Science Hong Kong Research Grant Council - No. CUHK7422/03M; No. 2140564 ark:/67375/WNG-ZXGW6NCX-V ArticleID:PMIC200800155 Both these authors contributed equally to this paper. Additional corresponding author ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1615-9853 1615-9861 |
DOI: | 10.1002/pmic.200800155 |