Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham), inhibit activation of nuclear factor-kappaB by inhibiting both its nuclear localization and ability to bind DNA.

Abstract

Triterpenoid saponins, which are present in leguminous plants and some marine animals, possess a broad range of biological actions. We have earlier reported the extraction of avicins, a family of triterpenoid saponins obtained from the Australian desert tree Acacia victoriae (Leguminosae: Mimosoideae) that inhibit tumor cell growth and induce apoptosis, in part, by perturbing mitochondrial function. These saponins have also been found to prevent chemical-induced carcinogenesis in mice. This study examines the effect of a triterpene mixture (F094) and a single molecular species (avicin G) isolated from the mixture on tumor necrosis factor (TNF)-induced activation of nuclear transcription factor-kappaB (NF-kappaB) in Jurkat cells (human T cell leukemia). Both F094 and avicin G were found to be potent inhibitors of TNF-induced NF-kappaB. Treatment of Jurkat cells with avicin G resulted in a much slower accumulation of the p65 subunit of NF-kappaB into the nucleus whereas the degradation of IkappaBalpha was unaffected. Avicin G also impaired the binding of NF-kappaB to DNA in in vitro binding assays. Treatment of cells with DTT totally reversed the avicin G-induced inhibition of NF-kappaB activity, suggesting that sulfhydryl groups critical for NF-kappaB activation were being affected. Avicin G treatment resulted in decreased expression of NF-kappaB-regulated proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Thus, the avicins may prove important for reducing both oxidative and nitrosative cellular stress and thereby suppressing the development of malignancies and related diseases.

• Authors: V Haridas, C J Arntzen, J U Gutterman
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 98 Issue 20 Pg. 11557-62 (Sep 25 2001) ISSN: 0027-8424 [Print] United States
• PMID: 11572998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• Isoenzymes
• Membrane Proteins
• NF-kappa B
• Saponins
• Tumor Necrosis Factor-alpha
• Luciferases
• NOS2 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Acacia (therapeutic use)
• Animals
• Cell Line
• Cell Nucleus (metabolism)
• Cyclooxygenase 2
• DNA, Neoplasm (metabolism)
• Gene Expression Regulation, Enzymologic
• Humans
• Isoenzymes (genetics)
• Jurkat Cells
• Luciferases (genetics)
• Membrane Proteins
• Mice
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase (genetics)
• Nitric Oxide Synthase Type II
• Phytotherapy
• Prostaglandin-Endoperoxide Synthases (genetics)
• Saponins (therapeutic use)
• Tumor Necrosis Factor-alpha (pharmacology)