Induction of leukemia cell apoptosis by cheliensisin A involves down-regulation of Bcl-2 expression
Zhong, L; Li, CM; Hao, XJ; Lou, LG
2005-05-01
发表期刊ACTA PHARMACOLOGICA SINICA
卷号26期号:5页码:623-628
摘要Aim: To investigate the apoptosis-inducing effect of cheliensisin A (GC-51), a novel styryl-lactone isolated from Goniothalamus cheliensis, on human promyelocytic leukemia HL-60 cells and the mechanism of action involved. Methods: Apoptotic cell death was determined by morphological examination and DNA agarose gel electrophoresis. The activity of caspase-3 was assessed using Western blotting and the expression of Bcl-2 and Bax genes was analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) method. Results: GC-51 significantly inhibited the proliferation of HL-60 cells with an IC50 of 2.4± 0. 2 μ mol/L and effectively induced apoptosis in HL-60 cells. Exposure of HL-60 cells to 10 μ mol/L GC-51 for 8 h resulted in approximately 53% of the cells undergoing apoptosis. Caspase-3 was activated in GC-51-treated cells, which was manifested by the appearance of the 17 kDa active form of caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP). Meanwhile, GC-51 markedly reduced the expression of the anti-apoptotic gene Bcl-2 and increased the expression of the pro-apoptotic gene Bax. The apoptosis-inducing effect of GC-51 was cAMP-dependent protein kinase (PKA) dependent because PKA, but not the protein kinase C, specific inhibitor H-89, blocked the induction of apoptosis by GC-51 in HL-60 cells. Conclusion: The results demonstrate that GC-51 effectively induces apoptosis in HL-60 cells and that this effect is PKA-dependent and involves the downregulation of Bcl-2 expression and the activation of caspase-3.
关键词Goniothalamus Cheliensis Cheliensisin a Apoptosis Hl-60 Cells Bcl-2 Genes Cyclic Amp-dependent Protein Kinases Caspases
学科领域Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
DOI10.1111/j.1745-7254.2005.00077.x
收录类别SCI
语种英语
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号WOS:000229103500019
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被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/14569
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Shanghai Inst Biol Sci, Inst Mat Med, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, Kunming 650204, Peoples R China
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Zhong, L,Li, CM,Hao, XJ,et al. Induction of leukemia cell apoptosis by cheliensisin A involves down-regulation of Bcl-2 expression[J]. ACTA PHARMACOLOGICA SINICA,2005,26(5):623-628.
APA Zhong, L,Li, CM,Hao, XJ,&Lou, LG.(2005).Induction of leukemia cell apoptosis by cheliensisin A involves down-regulation of Bcl-2 expression.ACTA PHARMACOLOGICA SINICA,26(5),623-628.
MLA Zhong, L,et al."Induction of leukemia cell apoptosis by cheliensisin A involves down-regulation of Bcl-2 expression".ACTA PHARMACOLOGICA SINICA 26.5(2005):623-628.
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