Proteomic identification of molecular targets of gambogic acid: Role of stathmin in hepatocellular carcinoma

Xin Wang, Yangchao Chen, Quan-bin Han, Chu-yan Chan, Hua Wang, Zheng Liu, Christopher Hon-ki Cheng, David T. Yew, Marie C.M. Lin, Ming-liang He, Hong-xi Xu*, Joseph J.Y. Sung, Hsiang-fu Kung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

73 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to) 242 - 253
JournalProteomics
Volume9
Issue number2
DOIs
Publication statusPublished - Jan 2009

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