Acetyl-11-Keto-ß-Boswellic Acid (Akba) is Cytotoxic for Meningioma Cells and Inhibits Phosphorylation of the Extracellular-Signal Regulated Kinase 1 and 2
Acetyl-l1-keto-13-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 RM. 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.
KeywordsAlbumin DMSO Tyrosine Leukemia Stein
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- 10.T. Inamura, M. Abe, K. Ikezaki, and M. Fukui, Leukotriene C4 contents, synthase and catabolic activity in human meningiomas, Neurological Res. 14:405–410 (1992).Google Scholar
- 14.H. Safayhi, T. Mack, J. Sabieraj, M.I. Anazodo, L.R. Subramanian, and H.P. Ammon, Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase, J Pharmacol Exper Therap. 261:1143–1146 (1992).Google Scholar
- 15.E.R. Sailer, S. Schweizer, S.E. Boden, H.P. Ammon, and H. Safayhi, Characterization of an acetyl-1lketo-13-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling, EurJBiochem. 256:364–368 (1998).Google Scholar
- 18.R.F. Hoernlein, T. Orlikowsky, C. Zehrer, D. Niethammer, E.R. Sailer, T. Simmet, G.E. Dannecker, and H.P.T. Ammon, Acetyl-11-keto-13-boswellic acid induced apoptosis in HL60 and CCRF-CEM cells and inhibits topoisomerase I, JPharm Exp Ther. 288:613–619 (1999).Google Scholar
- 21.B. Buechele, T. Syrovets, E. Gedek, and T. Simmet, Molecular interactions of human topoisomerase I and IIa with boswellic acid as analyzed by surface plasmon resonance, Suppl to Naunyn-S Arch Pharmacol. 359:R8–19, (Abstract) (1999).Google Scholar
- 22.C-L. Yu, M.H. Tsai, and D.W. Stacey, Serum stimulation of NIH3T3 cells induces the production of lipids able to inhibit GTPase-activating protein activity, Mol Cell Biol. 10:6683–6689 (1990).Google Scholar
- 23.I. Gupta, A. Parihar, P. Malhotra, G.B. Singh, R. Luedtke, H. Safayhi, and H.P.T. Ammon, Effects of Boswellia serrata gum resin in patients with ulcerative colitis, EurJMed Res. 2:37–43 (1997).Google Scholar
- 25.J.S. Sebolt-Leopold, D.T. Dudley, R. Herrera, K. van Becelaere, A. Wiland, R.C. Gowan, H. Tecle, S.D. Barrett, A. Bridges, S. Przybranowski, W.R. Leopold, and A.R. Saltiel, Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo, Nature Med. 5:810–816 (1999).PubMedCrossRefGoogle Scholar
- 26.I. Gupta, V. Gupta, A. Parihar, S. Gupta, R. Luedtke, H. Safayhi, and H.P.T. Ammon, Effects of Boswellia serrata gum resin in patients with bronchial asthma: Results of a double-blind, placebo-controlled, 6-week clinical study, EurJMed Res. 3:1–5 (1998).Google Scholar
- 27.D-K. Boeker, and M. Winking, Die Rolle von Boswellia-Sauren in der Therapie maligner Gliome, Deutsches Arzteblatt 94:A1197–A1199 (1997).Google Scholar
- 28.www.medizin.uni-tuebingen.de/--webnonk/clinical.html www.medizin.uni-tuebingen.de/--webnonk/clinical.htmlGoogle Scholar