Document Detail


Rhabdastrellic acid-A inhibited PI3K/Akt pathway and induced apoptosis in human leukemia HL-60 cells.
MedLine Citation:
PMID:  17920303     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increasing evidence suggests that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer treatment. Our investigation indicates that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge, Rhabdastrella globostellata, inhibits proliferation of HL-60 cells with an IC(50) value of 0.68mug/ml, and induces apoptosis. Rhabdastrellic acid-A also induces cleavage of the death substrate poly (ADP-ribose) polymerase (PARP) and caspase-3. Pretreatment of HL-60 cells with the caspase-3 specific inhibitor, DEVD-CHO, prevents Rhabdastrellic acid-A-induced DNA fragmentation and PARP cleavage. Activated PI3K and Akt significantly decreases after treatment with Rhabdastrellic acid-A in HL-60 cells. Expression levels of protein bcl-2, bax remain unchanged in response to Rhabdastrellic acid-A treatment in HL-60 cells. These results suggest that Rhabdastrellic acid-A inhibits PI3K/Akt pathway and induces caspase-3 dependent-apoptosis in HL-60 human leukemia cells.
Authors:
Jing-Feng Guo; Jun-Min Zhou; Yong Zhang; Rong Deng; Jian-Nan Liu; Gong-Kan Feng; Zong-Chao Liu; Ding-Jun Xiao; Song-Zhi Deng; Xiao-Feng Zhu
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Publication Detail:
Type:  Journal Article     Date:  2007-09-01
Journal Detail:
Title:  Cell biology international     Volume:  32     ISSN:  1065-6995     ISO Abbreviation:  Cell Biol. Int.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-02-22     Completed Date:  2008-06-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  48-54     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou 510060, PR China.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors*
Apoptosis / drug effects*
Caspase 3 / antagonists & inhibitors,  metabolism
DNA Damage
Down-Regulation
Enzyme Activation
HL-60 Cells
Humans
Oligopeptides / pharmacology
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Signal Transduction / drug effects*
Triterpenes / pharmacology*
bcl-2-Associated X Protein / biosynthesis
Chemical
Reg. No./Substance:
0/BAX protein, human; 0/Oligopeptides; 0/Proto-Oncogene Proteins c-bcl-2; 0/Triterpenes; 0/aspartyl-glutamyl-valyl-aspartal; 0/bcl-2-Associated X Protein; 0/rhabdastrellic acid A; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspase 3

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