Document Detail


Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells.
MedLine Citation:
PMID:  18281494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acetyl-keto-beta-boswellic acid (AKBA), a triterpenoid isolated from Boswellia carterri Birdw and Boswellia serrata, has been found to inhibit tumor cell growth and to induce apoptosis. The apoptotic effects and the mechanisms of action of AKBA were studied in LNCaP and PC-3 human prostate cancer cells. AKBA induced apoptosis in both cell lines at concentrations above 10 microg/mL. AKBA-induced apoptosis was correlated with the activation of caspase-3 and caspase-8 as well as with poly(ADP)ribose polymerase (PARP) cleavage. The activation of caspase-8 was correlated with increased levels of death receptor (DR) 5 but not of Fas or DR4. AKBA-induced apoptosis, caspase-8 activation, and PARP cleavage were inhibited by knocking down DR5 using a small hairpin RNA. AKBA treatment increased the levels of CAAT/enhancer binding protein homologous protein (CHOP) and activated a DR5 promoter reporter but did not activate a DR5 promoter reporter with the mutant CHOP binding site. These results suggest that AKBA induces apoptosis in prostate cancer cells through a DR5-mediated pathway, which probably involves the induced expression of CHOP.
Authors:
Min Lu; Lijuan Xia; Huiming Hua; Yongkui Jing
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer research     Volume:  68     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-18     Completed Date:  2008-03-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1180-6     Citation Subset:  IM    
Affiliation:
Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029-6547, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Binding Sites
CCAAT-Enhancer-Binding Proteins / biosynthesis,  metabolism
Caspase 3 / metabolism
Caspase 8 / metabolism
Cell Growth Processes / drug effects
Cell Line, Tumor
Enzyme Activation
Humans
Male
Neoplasms, Hormone-Dependent / drug therapy*,  genetics,  metabolism,  pathology
Promoter Regions, Genetic
Prostatic Neoplasms / drug therapy*,  genetics,  metabolism,  pathology
RNA, Messenger / biosynthesis,  genetics
RNA, Small Interfering / genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis,  genetics,  metabolism*
TNF-Related Apoptosis-Inducing Ligand / metabolism
Triterpenes / pharmacology*
Up-Regulation
Grant Support
ID/Acronym/Agency:
R21AT001539/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Triterpenes; 0/acetyl-11-ketoboswellic acid; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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