Estrogenic and anticarcinogenic properties of kurarinone, a lavandulyl flavanone from the roots of Sophora flavescens
ABSTRACT Kurarinone, a lavandulyl flavanone, was isolated from a polyphenolic extract of the roots of Sophora flavescens using fractionation guided by estrogenic activity, which was determined by recombinant yeast and Ishikawa Var-I bioassays. Kurarinone showed weak estrogenic activity both in the yeast screen and in the Ishikawa Var-I assay with EC(50) values of 4.6 and 1.66 microM, respectively. Furthermore, kurarinone was found to have potent cytotoxic activity (IC(50) value = 22.2 microM) against human MCF-7/6 breast cancer cells in the sulforhodamine-B assay.
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ABSTRACT: This study was designed to investigate the effects of the prenylated flavonoid kurarinone on TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis and its underlying mechanism. A low dose of kurarinone had no significant effect on apoptosis, but this compound markedly promoted tumor cell death through elevation of Bid cleavage, cytochrome c release and caspase activation in HeLa cells treated with TRAIL. Caspase inhibitors inhibited kurarinone-mediated cell death, which indicates that the cytotoxic effect of this compound is mediated by caspasedependent apoptosis. The cytotoxic effect of kurarinone was not associated with expression levels of Bcl-2 and IAP family proteins, such as Bcl-2, Bcl-xL, Bid, Bad, Bax, XIAP, cIAP-1 and cIAP-2. In addition, this compound did not regulate the deathinducing receptors DR4 and DR5. On the other hand, kurarinone significantly inhibited TRAIL-induced IKK activation, IκB degradation and nuclear translocation of NF-κB, as well as effectively suppressed cellular FLICE-inhibitory protein long form (cFLIPL) expression. The synergistic effects of kurarinone on TRAIL-induced apoptosis were mimicked when kurarinone was replaced by the NF-κB inhibitor withaferin A or following siRNA-mediated knockdown of cFLIPL. Moreover, cFLIP overexpression effectively antagonized kurarinone-mediated TRAIL sensitization. These data suggest that kurarinone sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent cFLIP expression, indicating that this compound can be used as an anti-tumor agent in combination with TRAIL.Experimental and Molecular Medicine 08/2012; 44(11). DOI:10.3858/emm.2012.44.11.074 · 2.46 Impact Factor
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ABSTRACT: Prenylated flavonoids are natural compounds that often represent the active components in various medicinal plants and exhibit beneficial effects on human health. Prenylated flavonoids are hybrid products composed of a flavonoid core mainly attached to either 5-carbon (dimethylallyl) or 10-carbon (geranyl) prenyl groups derived from isoprenoid (terpenoid) metabolism, and the prenyl groups are crucial for their biological activity. Prenylation reactions in vivo are crucial coupling processes of two major metabolic pathways, the shikimate-acetate and isoprenoid pathways, in which these reactions are also known as a rate-limiting step. However, none of the genes responsible for the prenylation of flavonoids has been identified despite more than 30 years of research in this field. We have isolated a prenyltransferase gene from Sophora flavescens, SfN8DT-1, responsible for the prenylation of the flavonoid naringenin at the 8-position, which is specific for flavanones and dimethylallyl diphosphate as substrates. Phylogenetic analysis shows that SfN8DT-1 has the same evolutionary origin as prenyltransferases for vitamin E and plastoquinone. The gene expression of SfN8DT-1 is strictly limited to the root bark where prenylated flavonoids are solely accumulated in planta. The ectopic expression of SfN8DT-1 in Arabidopsis thaliana resulted in the formation of prenylated apigenin, quercetin, and kaempferol, as well as 8-prenylnaringenin. SfN8DT-1 represents the first flavonoid-specific prenyltransferase identified in plants and paves the way for the identification and characterization of further genes responsible for the production of this large and important class of secondary metabolites.Plant physiology 04/2008; 146(3):1075-84. DOI:10.1104/pp.107.110544 · 7.39 Impact Factor
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ABSTRACT: 7,9,2′,4′-Tetrahydroxy-8-isopentenyl-5-methoxychalcone (THIPMC), isolated from the roots of Sophora flavescens Ait., was found to be active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), either alone or in combination with ampicillin (AM) or gentamicin (GM), vis checkerboard assay. Minimum inhibitory concentrations ranged from 1 to 8 μg/mL for THIPMC, from 128 to 1024 μg/mL for AM, and from 128 to 512 μg/ mL for GM, respectively. The combinations of THIPMC plus AM or GM yielded a fractional inhibitory concentration index ranging from 0.188 to 0.375 μg/mL, thereby indicating a synergistic effect. These findings suggest that THIPMC alone or in combination with antibiotics against MRSA might be useful for controlling MRSA infections. However, VRE infection was only effectively treated by THIPMC alone.Journal of the Korean Society for Applied Biological Chemistry 53(3). DOI:10.3839/jksabc.2010.045 · 0.54 Impact Factor