Document Detail

Gambogic acid induces apoptosis by regulating the expression of Bax and Bcl-2 and enhancing caspase-3 activity in human malignant melanoma A375 cells.
MedLine Citation:
PMID:  19200201     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: To investigate the effect of a Chinese traditional medicine, gambogic acid (GA), on human malignant melanoma (MM) A375 cells and to study the mechanism of apoptosis induced by GA. METHODS: A375 cells were treated with GA at different doses and for different times, and their proliferation and viability were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis induced by GA in A375 cells was observed by annexin-V/propidium iodide doubling staining flow cytometry assay and Hoechst staining. To further determine the molecular mechanism of apoptosis induced by GA, the changes in expression of Bcl-2 and Bax were detected by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, and caspase-3 activity was measured by fluorescence resonance energy transfer (FRET) probe. RESULTS: After incubation with GA, A375 cell proliferation was dramatically inhibited in a dose-dependent manner. After these cells had been exposed to GA for 24, 36 and 48 h, the IC(50) values were 1.57 +/- 0.05, 1.31 +/- 0.20, and 1.12 +/- 0.19 microg/mL, respectively. Treatment of A375 cells with GA (2.5-7.5 microg/mL) for 36 h resulted in an increased number of early apoptotic cells, which ranged from 27.6% to 41.9%, in a dose-dependent manner, compared with only 3.5% apoptotic cells in the non-GA-treated group. An increase in Bax and decrease in Bcl-2 expression were found by real-time RT-PCR and Western blot. Caspase-3 activity was increased in a dose-dependent manner, observed by FRET probe. CONCLUSION: GA can inhibit the proliferation of A375 cells and induce their apoptosis, which may be related to the up-regulation of the Bax/Bcl-2 ratio and caspase-3 activity.
Xiaoyuan Xu; Yeqiang Liu; Ling Wang; Jun He; Hongfeng Zhang; Xinxiang Chen; Yan Li; Jing Yang; Juan Tao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of dermatology     Volume:  48     ISSN:  1365-4632     ISO Abbreviation:  Int. J. Dermatol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-09     Completed Date:  2009-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243704     Medline TA:  Int J Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  186-92     Citation Subset:  IM    
Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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MeSH Terms
Apoptosis / drug effects*,  physiology
Caspase 3 / metabolism*
Cell Line, Tumor
Cell Survival / drug effects,  physiology
Dose-Response Relationship, Drug
Fluorescence Resonance Energy Transfer
Gene Expression Regulation, Neoplastic / drug effects
Melanoma / drug therapy*,  pathology,  physiopathology
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism
RNA, Messenger / metabolism
Skin Neoplasms / drug therapy*,  pathology,  physiopathology
Xanthones / pharmacology*
bcl-2-Associated X Protein / genetics,  metabolism
Reg. No./Substance:
0/BAX protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Xanthones; 0/bcl-2-Associated X Protein; 2752-65-0/gambogic acid; EC 3.4.22.-/Caspase 3

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