Acetyl-11-keto-β-boswellic acid (AKBA), a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata (frankincense), is a Nrf2 activator against a large number of inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn’s disease, and bronchial asthma[3]. AKBA is as a novel, orally active, non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro[4]. AKBA enhances apoptosis induced by cytokines and chemotherapeutic agents, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-κB-regulated gene expression[3]. In tumor cells, AKBA suppressed both inducible and constitutive NF-κB activation examined by DNA binding. AKBA inhibited the TNF-induced activation of IκBα kinase (IKK), IκBα phosphorylation, IκBα ubiquitination, IκBα degradation, p65 phosphorylation, and p65 nuclear translocation[3]. AKBA inhibited the NF-κB-dependent reporter gene expression activated by TNFR type 1, TNFR-associated death domain protein, TNFR-associated factor 2, NF-κB-inducing kinase, and IKK[3]. Induction of apoptosis in HL-60 and CCRF-CEM by AKBA may be due to inhibition of topoisomerase I in these cells[5]. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA), whose inhibitory effect on tumor growth was well correlated with suppression of angiogenesis induced by VEGFR2 signaling pathways[6]. In mice, AKBA significantly inhibited blood vessel formation in the Matrigel plug assay and effectively suppressed vascular endothelial growth factor (VEGF)–induced microvessel sprouting in rat aortic ring assay ex vivo[6]. In vitro, AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) kinase (KDR/Flk-1) with IC50 of 1.68 μmol/L[6]. At low micromolar concentrations, AKBA rapidly and potently inhibited the phosphorylation of Erk-1/2 and impaired the motility of meningioma cells[7]. AKBA inhibits the motility of meningioma cells showing a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2 - 8 μM[7].
搜索
