Phaseollin

Estrogenic and antiestrogenic activities of phytoalexins from red kidney bean (Phaseolus vulgaris L.).[Pubmed:21133423]

J Agric Food Chem. 2011 Jan 12;59(1):112-20.

Legumes are the predominant source of isoflavones considered to be phytoestrogens that mimic the hormone 17beta-estradiol (E2). Due to the risks associated with hormone replacement therapy, there is a growing need for alternative sources of estrogenic formulations for the treatment of menopausal symptoms. Legume phytoalexins (induced isoflavones) are produced under conditions of stress that include insect damage, wounding, or application of elicitors. The estrogenic and antiestrogenic activities of methanolic extracts obtained from red kidney bean treated with the fungus Aspergillus sojae were compared with those of untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay. A. sojae-treated red kidney bean extracts displayed both estrogenic and antiestrogenic activities. Analysis of elicitor-treated red kidney bean extracts showed that A. sojae treatments achieved maximal levels of kievitone at 1199 +/- 101 mug/g and Phaseollin at 227.8 +/- 44 mug/g. The phytoalexins kievitone and Phaseollin were isolated from A. sojae-treated red kidney bean extracts and analyzed for estrogenic activity using ERalpha and ERbeta binding, ERE luciferase assays in MCF-7 and HEK 293 cells, and MCF-7 cell proliferation. Kievitone showed the highest relative binding affinity to ERalpha with kievitone (0.48%) > Phaseollin (0.21%), and Phaseollin showed the highest relative binding affinity to ERbeta with Phaseollin (0.53%) > kievitone (0.42%). In an ERE luciferase assay in MCF-7 cells, kievitone displayed high ER transactivation at 10 muM; Phaseollin displayed low ER transactivation. Both kievitone and Phaseollin stimulated MCF-7 cell proliferation, with kievitone displaying agonist activity between 0.1 and 10 muM. Cotransfection reporter assays performed in HEK 293 demonstrated that Phaseollin selectively increased ERE transcriptional activity of ERbeta and kievitone selectively increased ERE transcriptional activity of ERalpha. Although Phaseollin displayed attenuation of ER transactivation in the ERE luciferase assay in MCF-7 cells, both phytoalexins attenuated the effects of E2 in an MCF-7 cell colonial survival assay. This work provides evidence that the red kidney bean phytoalexins kievitone and Phaseollin possess both estrogenic and antiestrogenic activities.

Pterocarpans phaseollin and neorautenol isolated from Erythrina addisoniae induce apoptotic cell death accompanied by inhibition of ERK phosphorylation.[Pubmed:17964704]

Toxicology. 2007 Dec 5;242(1-3):71-9.

The genus Erythrina (Leguminosae), consisting of over 100 different species, is distributed in tropical regions. In traditional medicine, Erythrina species are used to treat cancer, but little is known about the anticancer mechanisms. From the stem bark of Erythrina addisoniae Hutch. & Dalziel, six prenylated pterocarpans were isolated and analysed for pharmacological activity: While calopocarpin, cristacarpin, orientanol c, and isoneorautenol showed only a weak or moderate toxicity in H4IIE hepatoma cells (EC(50)-value> 25 microM), the toxicity of neorautenol and Phaseollin was in the low micromolar range (EC(50)-value: 1 and 1.5 microM, respectively). We further focused on these two substances showing that both increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Neorautenol (10 microM, 2h), but not Phaseollin induced the formation of DNA strand breaks (comet assay). Both substances showed no effect on NF-kappaB signalling (SEAP assay: basal activity and stimulation with TNF-alpha), on the other hand both pterocarpans (10 microM, 2 h) decreased the activation of the ERK kinase (p44/p42), an mitogen activated protein kinase which is associated with cell proliferation. We conclude that the pterocarpans Phaseollin and neorautenol may be responsible for the anticarcinogenic actions of the plant extract reported in the literature. Further analysis of these substances may lead to new pharmacons to be used in cancer therapy.

The induction of phenylalanine ammonia lyase and phaseollin by 9-aminoacridine and other deoxyribonucleic Acid intercalating compounds.[Pubmed:16657762]

Plant Physiol. 1971 Aug;48(2):197-202.

Bean pod tissue (Phaseolus vulgaris L. var. Top Crop) is induced to produce Phaseollin when challenged with various microorganisms. The pods react in the same manner when challenged with 9-aminoacridine. This compound also caused an increase in concentrations of phenylalanine ammonia lyase, an enzyme of the Phaseollin synthesizing pathway. Both the synthesis of phenylalanine ammonia lyase and Phaseollin are subject to inhibition by actinomycin D, cycloheximide, or 6-methylpurine. The results suggest that both Phaseollin production and increased phenylalanine ammonia lyase, when induced by 9-aminoacridine, require newly synthesized RNA and protein.The concentration of 9-aminoacridine optimal for synthesis of Phaseollin and PAL (0.5 mg/ml) does not increase the rate of total protein synthesis. However, there is a differential effect of 9-aminoacridine on synthesis of certain protein fractions. Optimal concentrations of 9-aminoacridine induce Phaseollin and phenylalanine ammonia lyase synthesis while reducing the net synthesis of RNA during the period of induction.The planar three-ring structure of 9-aminoacridine appears to be a desirable feature for Phaseollin and phenylalanine ammonia lyase induction. Similar compounds, all DNA intercalators, having dimethylamino, diethylamino, amino, or 9-alkylamino substitutions of a three-ring acridine skeleton, are also inducers of phenylalanine ammonia lyase and Phaseollin synthesis.It is suggested that 9-aminoacridine and other DNA intercalators function as inducers of Phaseollin and phenylalanine ammonia lyase synthesis by reacting with the DNA template.