We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Induction of leukemia cell apoptosis by cheliensisin A involves downregulation ofBcl-2expression.
- Authors
Li Zhong; Chao-Ming Li; Xiao-Jiang Hao; Li-Guang Lou
- Abstract
To investigate the apoptosis-inducing effect of cheliensisin A (GC-51), a novel styryl-lactone isolated fromGoniothalamus cheliensis, on human promyelocytic leukemia HL-60 cells and the mechanism of action involved.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 ofBcl-2andBaxgenes was analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) method.GC-51 significantly inhibited the proliferation of HL-60 cells with an IC50 of 2.4±0. 2 imol/L and effectively induced apoptosis in HL-60 cells. Exposure of HL-60 cells to 10 imol/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 geneBcl-2and increased the expression of the pro-apoptotic geneBax.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.The results demonstrate that GC-51 effectively induces apoptosis in HL-60 cells and that this effect is PKA-dependent and involves the downregulation ofBcl-2expression and the activation of caspase-3.
- Subjects
LEUKEMIA; APOPTOSIS; GENES; CYCLIC adenylic acid; PROTEIN kinases
- Publication
Acta Pharmacologica Sinica, 2005, Vol 26, Issue 5, p623
- ISSN
1671-4083
- Publication type
Article
- DOI
10.1111/j.1745-7254.2005.00077.x