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Acetyl-Keto-β-Boswellic Acid Induces Apoptosis through a Death Receptor 5–Mediated Pathway in Prostate Cancer Cells

¹ Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York and ² Shenyang Pharmaceutical University, Shenyang, China

Requests for reprints: Yongkui Jing, Division of Hematology/Oncology, Department of Medicine, Box 1178, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6547. Phone: 212-241-6775; Fax: 212-996-5787; E-mail: yongkui.jing{at}mssm.edu.

Key Words: acetyl-keto-β-boswellic acid • apoptosis • prostate cancer • death receptor 5

Acetyl-keto-β-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 µg/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. [Cancer Res 2008;68(4):1180–6]