title: Cytotoxic action of acetyl-11-keto-beta-boswellic acid (AKBA) on meningioma cells.
abstract: Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate of the tree Boswellia serrata (frankincense). Because pentacyclic triterpenes have antiproliferative and cytotoxic effects against different tumor types, we investigated whether AKBA would act in a similar fashion on primary human meningioma cell cultures. Primary cell cultures were established from surgically removed meningioma specimens. The number of viable cells in the absence/presence of AKBA was determined by the non-radioactive cell proliferation assay. The activation status of the proliferative cell marker, extracellular signal-regulated kinase-1 and -2 (Erk-1 and Erk-2) was determined by immunoblotting with the antibody that recognizes the activated form of these proteins. Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2 - 8 microM. At low micromolar concentrations, AKBA rapidly and potently inhibited the phosphorylation of Erk-1/2 and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB. The cytotoxic action of AKBA on meningioma cells may be mediated, at least in part, by the inhibition of the Erk signal transduction pathway. Because of the central role the Erk pathway plays in signal transduction and tumorigenesis, further investigation into the potential clinical use for AKBA and related boswellic acids is warranted.
authors.affiliation: Cleveland Clinic Foundation, Department of Neurosurgery, 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: Judy
authors.initials: J
authors.lastname: Bondar
authors.forename: Jyoti A
authors.initials: JA
authors.lastname: Harwalkar
authors.forename: Hasan
authors.initials: H
authors.lastname: Safayhi
authors.forename: Mladen
authors.initials: M
authors.lastname: Golubic
mesh_terms: D029743:Boswellia; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008579:Meningioma / Q000188:drug therapy / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases