Acetyl-11-Keto-ß-Boswellic Acid (Akba) is Cytotoxic for Meningioma Cells and Inhibits Phosphorylation of the Extracellular-Signal Regulated Kinase 1 and 2

Park, Yong Seok; Lee, Joung H.; Harwalkar, Jyoti A.; Bondar, Judy; Safayhi, H.; Golubić, Mladen

doi:10.1007/978-1-4615-0193-0_60

Cited by 58 publications

(24 citation statements)

References 18 publications

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“…71 To date, it is unclear whether high 5-LO expression is present in meningioma precursor (leptomeningeal) cells or is a characteristic only of meningiomas. These data indicate that 5-LO is overexpressed in high grade astrocytomas and possibly in meningiomas and support the notion that, in addition to COX-2 derived eicosanoids, 5-LO eicosanoids may also play a role in tumorigenesis and progression of these brain tumours.…”

Section: -Lipoxygenasementioning

confidence: 99%

The eicosanoid cascade: possible role in gliomas and meningiomas

Nathoo

2004

Journal of Clinical Pathology

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Section: -Lipoxygenasementioning

confidence: 99%

The eicosanoid cascade: possible role in gliomas and meningiomas

Nathoo

2004

Journal of Clinical Pathology

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“…AKBA is a naturally occurring pentacyclic triterepenic acid isolated from the gum resin exudate from the stem of the tree Boswellia serrata. AKBA has been recently identified as a novel, orally active, nonredox and noncompetitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro (Park et al, 2002). In humans, orally taken BE manifests as plasma KBA.…”

Section: Discussionmentioning

confidence: 99%

Human Genome Screen to Identify the Genetic Basis of the Anti-inflammatory Effects ofBoswelliain Microvascular Endothelial Cells

Roy

Khanna

Shah

et al. 2005

DNA and Cell Biology

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Inflammatory disorders represent a substantial health problem. Medicinal plants belonging to the Burseraceae family, including Boswellia, are especially known for their anti-inflammatory properties. The gum resin of Boswellia serrata contains boswellic acids, which inhibit leukotriene biosynthesis. A series of chronic inflammatory diseases are perpetuated by leukotrienes. Although Boswellia extract has proven to be anti-inflammatory in clinical trials, the underlying mechanisms remain to be characterized. TNF alpha represents one of the most widely recognized mediators of inflammation. One mechanism by which TNFalpha causes inflammation is by potently inducing the expression of adhesion molecules such as VCAM-1. We sought to test the genetic basis of the antiinflammatory effects of BE (standardized Boswellia extract, 5-Loxin) in a system of TNF alpha-induced gene expression in human microvascular endothelial cells. We conducted the first whole genome screen for TNF alpha- inducible genes in human microvascular cells (HMEC). Acutely, TNF alpha induced 522 genes and downregulated 141 genes in nine out of nine pairwise comparisons. Of the 522 genes induced by TNF alpha in HMEC, 113 genes were clearly sensitive to BE treatment. Such genes directly related to inflammation, cell adhesion, and proteolysis. The robust BE-sensitive candidate genes were then subjected to further processing for the identification of BE-sensitive signaling pathways. The use of resources such as GenMAPP, KEGG, and gene ontology led to the recognition of the primary BE-sensitive TNF alpha-inducible pathways. BE prevented the TNF alpha-induced expression of matrix metalloproteinases. BE also prevented the inducible expression of mediators of apoptosis. Most strikingly, however, TNF alpha-inducible expression of VCAM-1 and ICAM-1 were observed to be sensitive to BE. Realtime PCR studies showed that while TNF alpha potently induced VCAM-1 gene expression, BE completely prevented it. This result confirmed our microarray findings and built a compelling case for the anti-inflammatory property of BE. In an in vivo model of carrageenan-induced rat paw inflammation, we observed a significant antiinflammatory property of BE consistent with our in vitro findings. These findings warrant further research aimed at identifying the signaling mechanisms by which BE exerts its anti-inflammatory effects.

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“…The efficacy of curcumin in vivo is limited by its poor bioavailability; therefore, more stable curcumin derivatives are desirable and need to be studied. Using 11 primary human meningioma cell cultures Park et al [51] described potent cytotoxic activity of acetyl-11-keto-beta-boswellic acid, which rapidly and potently inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2.…”

Section: Plant-derived Agentsmentioning

confidence: 98%