title: Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells.
abstract: 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.affiliation: Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029-6547, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xia
authors.forename: Huiming
authors.initials: H
authors.lastname: Hua
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Jing
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D053148:Caspase 3; D053181:Caspase 8