Inhibition of Nuclear Factor-.KAPPA.B Activation by 2',8"-Biapigenin

Abstract

Chemoprevention is considered to be one of the most promising strategies for the prevention of human cancers. It is defined as the use of either natural or synthetic compounds to block or retard the carcinogenic process, and many natural candidates including epigallocatechin, genistein and sulforaphane have been evaluated in terms of malignancy prevention. 1-3)Recently, it was suggested that chronic inflammation is associated with carcinogenesis. 4,5) Chronic inflammation leads to the induction of specific enzymes in affected tissues and cells. In particular, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are responsible for the exaggerated production of NO and prostaglandins, respectively, and are believed to be involved in the pathogenesis of cancer.6,7) COX-2 expression increases during tumor progression in the stomach, suggesting that COX-2 participates in gastric tumorigenesis.8) It has also been reported that there is a strong positive relationship between the presence of iNOS and the frequency of mutation in colon tumor tissues. 9)Hence, the overproduction of prostaglandins and NO may act as both an endogenous initiator and as a promoter of carcinogenesis and specific inhibitors of COX-2 or iNOS might have applications as chemopreventive agents in human cancer. Lee et al. 10) reported that the water-extracted fraction of Selaginella tamariscina (Selaginellaceae) efficiently increased p53 gene expression and induced G1 arrest, suggesting that S. tamariscina is a candidate chemopreventive. Crude extracts of S. tamariscina also reduced the production of proinflammatory cytokines, interleukin-1b, and tumor necrosis factor-a in human mesangial cells.11) As a part of our program to screen for potential cancer chemopreventive compounds from medicinal plants, we isolated 2Ј,8Љ-biapigenin from S. tamariscina (Fig. 1). The biological activity of 2Ј,8Љ-biapigenin has not been studied.In the present study, we investigated the modulating effects of the bi-flavonoid, 2Ј,8Љ-biapigenin on the expressions and activities of iNOS and COX-2 induced by lipopolysaccharide (LPS) in Raw264.7 macrophage cells. We found that 2Ј,8Љ-biapigenin inhibited nuclear factor (NF)-kB activation, and that this action is required for its blocking effects on iNOS and COX-2. MATERIALS AND METHODS Extraction and Isolation of 2,8؆-Biapigenin WholeSelaginella tamariscina (600 g) was extracted with MeOH at room temperature to afford 50.5 g of residue. The methanol extract was suspended in water and then sequentially partitioned in dichloromethane, ethyl acetate, and n-butanol. Three grams of the EtOAc fraction was subjected to silica gel column chromatography using a CHCl 3 -MeOH-H 2 O (12 : 1 : 0.1→8 : 1 : 0.1→5 : 1 : 0.1→2 : 1 : 0.1→1 : 1 : 0.1→Me OH only) gradient elution system. Fractions were combined based on their TLC patterns to yield subfractions designated as E1-E10. Subfraction E4 (438.9 mg) was purified by Sephadex LH 20 column chromatography using MeOH : H 2 Oϭ2 : 1 as eluant to give four subfractions (E41-E44). ...

Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase‐2 and matrix metalloproteinase‐9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways

“…Such a decrease in phosphorylated IkBa in the cytosol in response to cranberry PACs treatment could potentially decrease the ability of p65 to translocate to the nucleus. In this regard, the effects of flavonoids upon various cancer cell lines, including DU145 human prostate cancer cells, have been examined and these studies have found a decrease in both NF-kB translocation and DNA binding after treatment with this class of compounds [Woo et al, 2006;Shen et al, 2010;Yun et al, 2009]. Recently, a study has shown that PACs from cranberries can affect both the expression and activity of select MMPs in vitro and in this study, cranberry derived PACs were able to inhibit the activation of p65 in human macrophages .…”

S-Phase Accumulation of Candida albicans by Anticandidal Effect of Amentoflavone Isolated from Selaginella tamariscina

“…The EtOAc fraction (3.0 g) was placed on a silica gel (300 g, 4.8ϫ45 cm) column and eluted using a C-NMR data, for amentoflavone, were identical to those reported in literature. 17,23,24) The Effects of Sodium Azide (NaN 3 ) on Antifungal Activity To investigate the effects of NaN 3 on the antifungal activity of amentoflavone in C. albicans, its activity was determined either in the absence or presence of 0.002% NaN 3 . The subcultured C. albicans cells were cultured at a half of MIC in the absence or presence of 0.002% NaN 3 .…”

Apigenin Blocks Lipopolysaccharide-Induced Lethality In Vivo and Proinflammatory Cytokines Expression by Inactivating NF-κB through the Suppression of p65 Phosphorylation

“…Notably, apigenin inhibits the production of IL-1␤ and TNF in mouse cells lines more effectively than resveratrol, another plant phenolic compound (22). Previous studies also showed that apigenin regulates prostaglandin and NO production in mouse cell lines through the regulation of NF-B (23). However, the molecular anti-inflammatory mechanisms of apigenin and its potential as an anti-inflammatory agent in vivo remain elusive.…”