| Gambogic acid induces apoptosis by regulating the expression of Bax and Bcl-2 and enhancing caspase-3 activity in human malignant melanoma A375 cells. | |
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MedLine Citation:
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PMID: 19200201 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiaoyuan Xu; Yeqiang Liu; Ling Wang; Jun He; Hongfeng Zhang; Xinxiang Chen; Yan Li; Jing Yang; Juan Tao |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of dermatology Volume: 48 ISSN: 1365-4632 ISO Abbreviation: Int. J. Dermatol. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-09 Completed Date: 2009-06-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0243704 Medline TA: Int J Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 186-92 Citation Subset: IM |
Affiliation:
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Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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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 Humans 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 |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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