title: Keto- and acetyl-keto-boswellic acids inhibit proliferation and induce apoptosis in Hep G2 cells via a caspase-8 dependent pathway.
abstract: Boswellic acids are the compounds isolated from the gum resin of Boswellia serrata and have been used for the treatment of inflammatory diseases for many years in the countries of the east. Recently, a few studies showed that the acids may have anti-cancer effect on leukemia and brain tumours. We investigated the apoptotic and anti-proliferative effects of two types of boswellic acids, keto-beta-boswellic acid and acetyl-keto-beta-boswellic acid, on liver cancer Hep G2 cells. After treating the cells with the boswellic acids, cell proliferation, DNA synthesis, and apoptosis were analysed. The activities of caspase-3, -8 and -9 were assayed. To explore the apoptotic pathway, specific caspase inhibitors were employed. It was found that boswellic acids decreased cell viability and [3H]thymidine incorporation, checked the cells in the G1 phase, and increased percentage of sub-G1. Boswellic acids strongly induced apoptosis accompanied by activation of caspase-3, -8 and -9. The apoptosis was blocked completely by caspase-8 or caspase-3 inhibitor, but inhibited partly by caspase-9 inhibitor. However, these caspase inhibitors did not show any effect on the alternations of cell viability caused by boswellic acids. In conclusion, boswellic acids have anti-proliferation and anti-cancer effects on Hep G2 cells. The apoptotic effect is mediated by a pathway dependent on caspase-8 activation. The acids may be a promising drug for the chemoprevention of liver cancer.
authors.affiliation: Biomedical Center, B11, Lund University, S-22184 Lund, Sweden.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Ake
authors.initials: A
authors.lastname: Nilsson
authors.forename: Stina
authors.initials: S
authors.lastname: Oredsson
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Duan
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D061945:Caspase Inhibitors; D014315:Triterpenes; C054625:boswellic acid; D004247:DNA; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases