title: Acetyl-11-keto-beta-boswellic acid (AKBA) is cytotoxic for meningioma cells and inhibits phosphorylation of the extracellular-signal regulated kinase 1 and 2.
abstract: Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata (frankincense). AKBA has been recently identified as a novel, orally active, non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro. Because natural pentacyclic triterpenes have an antiproliferative effect against different tumor types, we investigated the effects of AKBA on the proliferation of 11 primary cell cultures established from human surgical specimens of meningiomas, common central nervous system tumors. Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2-8 microM. At similar, physiologically achievable concentrations, AKBA rapidly (within minutes) and potently inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk-1 and Erk-2) in meningioma cells stimulated with platelet-derived growth factor BB. High expression level of 5-LO was detected in primary meningioma cells and surgical specimens by immunoblotting analysis, suggesting the possible role of 5-LO in meningioma tumorigenesis. Considering the critical importance of the Erk-1/2 signal transduction pathway not only in meningiomas but in other human neoplasms, the interruption of signaling through this evolutionarily conserved pathway might be one of the mechanisms by which AKBA induces suppression of proliferation and apoptosis of different tumor types.
authors.affiliation: Department of Neurosurgery, Cleveland Clinic Foundation, 9500 Euclid Avenue/NB2-120A, Cleveland, OH 44195, USA.
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Park
authors.forename: Joung H
authors.initials: JH
authors.lastname: Lee
authors.forename: Jyoti A
authors.initials: JA
authors.lastname: Harwalkar
authors.forename: Judy
authors.initials: J
authors.lastname: Bondar
authors.forename: Hasan
authors.initials: H
authors.lastname: Safayhi
authors.forename: Mladen
authors.initials: M
authors.lastname: Golubic
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008577:Meningeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008579:Meningioma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D012333:RNA, Messenger / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D001094:Arachidonate 5-Lipoxygenase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases