PMID- 11572998 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 98 IP - 20 DP - 2001 Sep 25 TI - 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. PG - 11557-62 AB - 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. FAU - Haridas, V AU - Haridas V AD - Department of Molecular Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. FAU - Arntzen, C J AU - Arntzen CJ FAU - Gutterman, J U AU - Gutterman JU LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (DNA, Neoplasm) RN - 0 (Isoenzymes) RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 0 (Saponins) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.13.12.- (Luciferases) RN - EC 1.14.13.39 (NOS2 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) SB - IM CIN - Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):10986-8. PMID: 11572955 MH - Acacia/*therapeutic use MH - Animals MH - Cell Line MH - Cell Nucleus/metabolism MH - Cyclooxygenase 2 MH - DNA, Neoplasm/metabolism MH - Gene Expression Regulation, Enzymologic MH - Humans MH - Isoenzymes/genetics MH - Jurkat Cells MH - Luciferases/genetics MH - Membrane Proteins MH - Mice MH - NF-kappa B/*antagonists & inhibitors/metabolism MH - Nitric Oxide Synthase/genetics MH - Nitric Oxide Synthase Type II MH - *Phytotherapy MH - Prostaglandin-Endoperoxide Synthases/genetics MH - Saponins/*therapeutic use MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC58768 EDAT- 2001/09/27 10:00 MHDA- 2002/01/05 10:01 PMCR- 2002/03/25 CRDT- 2001/09/27 10:00 PHST- 2001/09/27 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/09/27 10:00 [entrez] PHST- 2002/03/25 00:00 [pmc-release] AID - 98/20/11557 [pii] AID - 191363498 [pii] AID - 3634 [pii] AID - 10.1073/pnas.191363498 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11557-62. doi: 10.1073/pnas.191363498.