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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 20; pp. 11557 - 11562
• Main Authors: Haridas, Valsala, Arntzen, Charles J., Gutterman, Jordan U.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences 25.09.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Acacia victoriae; Antibodies; Apoptosis; avicins; Biological Sciences; Carcinogenesis; Cell lines; Cell nucleus; cyclooxygenase 2; DNA; Gels; Inflammation; Saponins; T lymphocytes; triterpenoid saponins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.191363498

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.