Avicins, A Family of Triterpenoid Saponins from Acacia victoriae (Bentham), Inhibit Activation of Nuclear Factor-κB by Inhibiting Both Its Nuclear Localization and Ability to Bind DNA
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: Mimosoidea...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 20; pp. 11557 - 11562 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
National Academy of Sciences
25.09.2001
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | 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-κB (NF-κB) in Jurkat cells (human T cell leukemia). Both F094 and avicin G were found to be potent inhibitors of TNF-induced NF-κB. Treatment of Jurkat cells with avicin G resulted in a much slower accumulation of the p65 subunit of NF-κB into the nucleus whereas the degradation of IκBα was unaffected. Avicin G also impaired the binding of NF-κB to DNA in in vitro binding assays. Treatment of cells with DTT totally reversed the avicin G-induced inhibition of NF-κB activity, suggesting that sulfhydryl groups critical for NF-κB activation were being affected. Avicin G treatment resulted in decreased expression of NF-κB-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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Contributed by Charles J. Arntzen To whom reprint requests should be addressed at: Department of Molecular Therapeutics, Box 41, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail: jgutterm@mdanderson.org. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.191363498 |