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

Triterpenoid saponins, which are present in leguminous plants and some mari ne animals, possess a broad range of biological actions. We have earlier re ported the extraction of avicins, a family of triterpenoid saponins obtaine d from the Australian desert tree Acacia victoriae (Leguminosae: Mimosoidea e) that inhibit tumor cell growth and induce apoptosis, in part, by perturb ing 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) isola ted from the mixture on tumor necrosis factor (TNF)-induced activation of n uclear transcription factor-kappaB (NF-kappaB) in Jurkat cells (human T cel l leukemia). Both F094 and avicin G were found to be potent inhibitors of T NF-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 I kappaB alpha was unaffected. Avicin G also imp aired 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-K B activity, suggesting that sulfhydryl groups critical for NF-kappaB activa tion were being affected. Avicin G treatment resulted in decreased expressi on of NF-kappaB-regulated proteins such as inducible nitric oxide synthase (MOS) and cyclooxygenase (COX-2). Thus, the avicins may prove important for reducing both oxidative and nitrosative cellular stress and thereby suppre ssing the development of malignancies and related diseases.