GA3, a new gambogic acid derivative, exhibits potent antitumor activities in vitro via apoptosis-involved mechanisms
文献类型：期刊论文
| 作者 | Xie, Hua1 ; Qin, Yu-xin1; Zhou, Yun-long2; Tong, Lin-jiang1; Lin, Li-ping1; Geng, Mei-yu1; Duan, Wen-hu2; Ding, Jian1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2009-03 |
| 卷号 | 30期号:3页码:346-354 |
| 关键词 | gambogic acid GA3 antitumor apoptosis caspase Bcl-2 cytochrome c |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2009.3 |
| 文献子类 | Article |
| 英文摘要 | Aim: Gambogic acid (GA) is the major active ingredient of gamboge, which is secreted from a Chinese traditional medicine, Garcinia hanburyi, which possesses potent antitumor activity. GA3, a new GA derivative, has been shown to possess better water solubility than GA. The aim of the present study was to examine the antitumor activity of GA3 and the mechanism underlying it. Methods: The growth inhibition of cancer cell lines induced by GA3 was assessed using the SRB assay. DAPI staining, flow cytometry, a DNA fragment assay, and Western blot analysis were used to study the apoptotic mechanisms of GA3. Results: GA3 displayed wide cytotoxicity in diversified human cancer cell lines with a mean IC50 value of 2.15 mu mol/L. GA3 was also effective against multidrug resistant cells, with an average resistance factor (RF) that was much lower than that of the reference drug, doxorubicin. Mechanistic studies revealed that GA3-induced apoptosis in HL-60 cells proceeded via both extrinsic and intrinsic pathways, with caspase-8 functioning upstream of caspase-9. In addition, GA3-driven apoptotic events were associated with up-regulation of Bax, down-regulation of Bcl-2 and cleavage of Bid. Moreover, GA3 triggered cytochrome c release from the mitochondria, in particular bypassing the involvement of the mitochondrial membrane potential. Conclusion: Better solubility and a potential anti-MDR activity, combined with a comparable antitumor efficacy, make GA3 a potential drug candidate in cancer therapy that deserves further investigation. |
| WOS关键词 | DRUG DISCOVERY ; CELLS ; BAX ; PROTEIN ; TRANSLOCATION ; CYTOTOXICITY ; PATHWAY ; BINDING ; DOMAIN ; DEATH |
| 资助项目 | National Natural Science Foundation of China[30721005] ; Shanghai Postdoctoral Grant[05R214157] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3628634 |
| WOS记录号 | WOS:000264239600009 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279296]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Duan, Wen-hu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Med Chem, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xie, Hua,Qin, Yu-xin,Zhou, Yun-long,et al. GA3, a new gambogic acid derivative, exhibits potent antitumor activities in vitro via apoptosis-involved mechanisms[J]. ACTA PHARMACOLOGICA SINICA,2009,30(3):346-354. |
| APA | Xie, Hua.,Qin, Yu-xin.,Zhou, Yun-long.,Tong, Lin-jiang.,Lin, Li-ping.,...&Ding, Jian.(2009).GA3, a new gambogic acid derivative, exhibits potent antitumor activities in vitro via apoptosis-involved mechanisms.ACTA PHARMACOLOGICA SINICA,30(3),346-354. |
| MLA | Xie, Hua,et al."GA3, a new gambogic acid derivative, exhibits potent antitumor activities in vitro via apoptosis-involved mechanisms".ACTA PHARMACOLOGICA SINICA 30.3(2009):346-354. |
入库方式： OAI收割
来源：上海药物研究所
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