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61.
Genistein (5,7,4′-trihydroxyisoflavone) the common soy beans isoflavone has attracted scientific interest due to its antioxidant, estrogenic, antiangiogenic and aniticancer activities. The aim of the present study was to investigate the interaction of genistein with biological (erythrocyte) and model membranes (dimyristoyl- and dipalmitoylphosphatidylcholine). Using Laurdan and Prodan as fluorescent probes, we demonstrated phase behavior and membrane fluidity changes induced by genistein. ESR spectroscopy revealed alterations caused by genistein in membrane domains structure and mobility of spin probes with free radicals located at different depths of membrane. The method of ESR spectra decomposition and computer simulation of the recorded spectra were used in order to visualize domain coexistence by GHOST condensation method. Fluorescence and ESR spectroscopy experiments performed at different temperatures enabled us to observe the effect of isoflavone on phospholipid bilayers in either gel or liquid crystalline phase. It was concluded that genistein preferentially intercalated into lipid headgroup region, to some extent into polar–apolar interface and only in minimal degree into hydrophobic core of the membrane. According to our best knowledge this is the first study on modification of domain structure of membranes by genistein. 相似文献
62.
Mansour A Chang VT Srinivas S Harrison J Raveche E 《Cancer immunology, immunotherapy : CII》2007,56(4):501-514
The role of ZAP-70 expression on the ex vivo response of blood cells from CLL and PLL patients to a combination of fludarabine,
a purine analog, and genistein, a tyrosine kinase inhibitor was studied. Patient cells were studied for the expression of
ZAP-70 mRNA and its relation to the induction of apoptosis in response to treatment with genistein 15–60 μM and/or fludarabine
3 μM. The combination of genistein and fludarabine resulted in a significantly increased induction of apoptosis relative to
the fludarabine alone. The ex vivo patient cells with a high ZAP-70 expression underwent more apoptosis in response to genistein
than did patient cells with a low ZAP-70 mRNA expression. In contrast, basal IL-10 mRNA expression correlated negatively with
apoptosis induction in response to genistein (P < 0.01). These studies suggest that, in malignant B cells that express elevated levels of the ZAP-70 signaling molecule,
genistein may inhibit the ZAP-70 tyrosine kinase activity, resulting in cell death. The ZAP-70 may serve as a target for therapy.
In addition, these studies suggest that the IL-10 expression by malignant B cells may not only suppress anti-tumor T cell
responses in vivo, but also promote the survival of malignant B cells despite treatment with chemotherapeutic agents. 相似文献
63.
Kim HA Jeong KS Park DH Lee JA Jeong WI Kim YK 《Molecular and cellular biochemistry》2007,301(1-2):201-208
Heavy water labeling method was applied to measure the effect of genistein on mammary gland carcinogenesis by incoporating
2H from 2H2O into the deoxyribose (dR) moiety of purine deoxyribonucleotides in dividing cells. In the present study, we followed the
study design of Lamartiniere group to evaluate the efficacy of 2H2O labeling on the measurement of mammary gland carconogenesis. Female Sprague–Dawley rats were fed estrogen-free AIN-93G diet
starting 1 week before breeding and continuing through pregnancy and lactation. Female pups were assigned to the following
groups on postnatal day 16 and fed AIN-93G diet: vehicle (dimethylsulfoxide) (DMSO), genistein, and estradiol benzoate (EB).
On postnatal days 16, 18, and 20, female pups were injected subcutaneously with 500 μg genistein/g body wt, 500 ng EB/g body
wt, or an equivalent volume of the vehicle. At day 50 postpartum, half of each group were gavaged with 60 mg dimethylbenz[a]anthracene
(DMBA) in perila oil. After 1 week of DMBA treatment, all animals were labeled with 2H2O by administration of 4% 2H2O in drinking water after single intraperitonial bolus injection with 99.9% 2H2O until sacrifice on postnatal day 81. The time-dependent weight gains were observed in all groups throughout the experimental
period. The enrichment of body 2H2O was attained at 1.84–2.47% through oral administration of 2H2O. Mammary epithelial cell proliferation was measured by enrichment (EM1) of dA from rats. DMBA-treated groups showed higher
fractional synthesis than DMBA non-treated groups. The group exposed only to genistein showed significantly lower EM1 (1.46 ± 0.87%)
than those of control groups, i.e., the DMBA non-treated group (2.28 ± 0.29%) and the DMBA-treated group (2.32 ± 0.28%). Bromodeoxyuridine
(BrdU) immunostaining of mammary tissue revealed that genistein reduced proliferation of the mammary epithelial, and the number
of cells stained positive for BrdU both in DMBA-treated groups and DMBA non-treated groups. H&E staining of mammary epithelium
also showed that the exposure to genistein decreased proliferation of the mammary epithelium. The epithelium in the rats treated
with DMBA showed mostly multiple cell layers, in contrast to the mostly double layer shown in the DMBA non-treated rats. The
exposure to genistein in the prepubertal period inhibited mammary epithelial cell proliferation. In conclusion, the 2H2O labeling results were in good agreement with the results of BrdU incorporation and histomorphometry, which demonstrates
that 2H2O labeling can be used as a tool to measure carcinogenesis. 相似文献
64.
《Phytomedicine》2014,21(12):1498-1503
Phytoestrogen-rich Pueraria mirifica (PM) tuberous extract is a promising candidate for the development of anti-osteoporosis drugs for postmenopausal women, but its action has never been validated in humans or in non-human primates, which are more closely related to humans than rodents. In vitro study of non-human primate osteoblasts is thus fundamental to prepare for in vivo studies of phytoestrogen effects on primate bone. This study aimed to establish a culture system of baboon primary osteoblasts and to investigate the effects of PM extract and its phytoestrogens on these cells. Primary osteoblasts from adult baboon fibulae exhibited osteoblast characteristics in regard to proliferation, differentiation, mineralization, and estrogen receptor expression. They responded to 17β-estradiol by increased proliferation rate and mRNA levels of alkaline phosphatase (ALP), type I collagen, and osteocalcin. After being exposed for 48 h to 100 μg/ml PM extract, 1000 nM genistein, or 1000 nM puerarin, primary baboon osteoblasts markedly increased the rate of proliferation and mRNA levels of ALP and type I collagen without changes in Runx2, osterix, or osteocalcin expression. PM extract, genistein, and puerarin also decreased the RANKL/OPG ratio, suggesting that they could decrease osteoclast-mediated bone resorption. However, neither PM extract nor its phytoestrogens altered calcium deposition in osteoblast culture. In conclusion, we have established baboon primary osteoblast culture, which is a new tool for bone research and drug discovery. Furthermore, the present results provide substantial support for the potential of PM extract and its phytoestrogens to be developed as therapeutic agents against bone fragility. 相似文献
65.
Muthusamy VS Anand S Sangeetha KN Sujatha S Arun B Lakshmi BS 《Chemico-biological interactions》2008,174(1):69-78
Insulin resistance is a fundamental aspect for the etiology of non-insulin dependent diabetes mellitus (NIDDM) and has links with a wide array of secondary disorders including weight gain and obesity. The present study analyzes the effect of Cichorium intybus methanolic (CME) extract on glucose transport and adipocyte differentiation in 3T3-L1 cells by studying the radiolabelled glucose uptake and lipid accumulation assays, respectively. By performing detannification (CME/DT), the role of tannins present in CME on both the activities was evaluated. CME and CME/DT exhibited significant glucose uptake in 3T3-L1 adipocytes with a dose-dependent response. Glucose uptake profile in the presence of PI3K and IRTK inhibitors (Wortmannin and Genistein) substantiates the mechanism used by both the extracts. CME inhibited the differentiation of 3T3-L1 preadipocytes but failed to show glucose uptake in inhibitor treated cells. The activity exhibited by CME/DT is exactly vice versa to CME. Furthermore, the findings from PTP1B inhibition assay, mRNA and protein expression analysis revealed the unique behavior of CME and CME/DT. The duality exhibited by C. intybus through adipogenesis inhibition and PPARgamma up regulation is of interest. Current observation concludes that the activities possessed by C. intybus are highly desirable for the treatment of NIDDM because it reduces blood glucose levels without inducing adipogenesis in 3T3-L1 adipocytes. 相似文献
66.
Lo CS 《Cell biology international》1999,23(4):251-255
(Na(+)+K(+))-adenosine triphosphatase (NaK-ATPase), an ubiquitous membrane transport protein consisting of alpha and beta subunits, regulates Na(+)/K(+)fluxes and maintains many vital physiological functions, including cell growth. Results have indicated that platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) both enhance NaK-ATPase subunits. Genistein, an inhibitor of tyrosine phosphorylation, inhibits serum- and PDGF-BB-induced NaK-ATPase alpha(1)subunit protein levels without inhibiting IGF-I-induced NaK-ATPase alpha(1)subunit protein levels. These results indicate that PDGF-BB and IGF-I utilize separate signaling pathways to induce the synthesis of NaK-ATPase alpha(1)subunits. In addition, genistein failed to inhibit PDGF-BB-stimulated NaK-ATPase beta(1)subunit levels, suggesting that two separate pathways are involved to induce the synthesis of the NaK-ATPase alpha(1)and beta(1)subunits, respectively. 相似文献
67.
Szkudelska K Nogowski L Szkudelski T 《The Journal of steroid biochemistry and molecular biology》2008,109(1-2):108-114
Genistein is a phytoestrogen exerting numerous biological effects. Its direct influence on adipocyte metabolism and leptin secretion was previously demonstrated. This study aimed to determine whether genistein antagonizes the antilipolytic action of insulin in rat adipocytes. Freshly isolated adipose cells were incubated for 90 min with epinephrine, epinephrine with insulin and epinephrine with a specific inhibitor of protein kinase A (H-89) at different concentrations of genistein (0, 6.25, 12.5, 25, 50 and 100 μM). Genistein failed to affect epinephrine-induced glycerol release, however, the inhibitory action of insulin on epinephrine-induced lipolysis was significantly abrogated in cells exposed to the phytoestrogen (12.5–100 μM). The increase in insulin concentration did not suppress the genistein effect. Its inhibitory influence on the antilipolytic action of insulin was accompanied by a substantial rise in cAMP in adipocytes. This rise appeared despite the presence of 10 nM insulin in the incubation medium. Further experiments, in which insulin was replaced by H-89, revealed that the antilipolytic action of protein kinase A inhibitor on epinephrine-induced lipolysis was not affected by genistein. This means that genistein counteracted the antilipolytic action of insulin due to the increase in cAMP levels and activation of protein kinase A in adipocytes. The observed attenuation of the inhibitory effect of insulin on triglyceride breakdown evoked by genistein was not related to its estrogenic activities, as evidenced in experiments employing the intracellular estrogen receptor blocker, ICI 182,780. Moreover, it was found that genistein-induced impairment of the antilipolytic action of insulin was not accompanied by changes in the proportion between fatty acids and glycerol released from adipocytes. The ability of genistein to counteract the antilipolytic action of insulin may contribute to the decreased triglyceride accumulation in adipose tissue. 相似文献
68.
Genistein induces G<Subscript>2</Subscript>/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells 总被引:1,自引:0,他引:1
Genistein is an isoflavonoid present in soybeans that exhibits anti-carcinogenic effect. Several studies have shown that genistein can trigger G2/M cell cycle arrest and inhibit cell growth in human breast cancer cells. In the present study, we assessed the role of MEK-ERK cascade in regulation of genistein-mediated G2/M cell cycle arrest in the hormone-independent cell line MDA-MB-231. Flow cytometric analysis showed that treatment of MDA-MB-231 cells with genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle, with a parallel depletion of the percentage of cells in G0/G1. Genistein-mediated G2/M arrest was associated with a decrease in the protein levels of Cdk1, cyclinB1, and Cdc25C as determined by Western blot analysis. Genistein induced a slow and stable activation of phosphorylated ERK1/2 in a concentration- and time-dependent manner in MDA-MB-231 cells. MEK1/2-specific inhibitor PD98059 blocked genistein-induced activation of ERK1/2 and markedly attenuated genistein-induced G2/M arrest. Furthermore, genistein induced the expression of Ras and Raf-1 protein. Genistein also up-regulated steady-state levels of both c-Jun and c-Fos. PD98059 did not depress genistein-induced up-regulation of Ras and Raf-1 protein. However, it markedly blocked genistein-induced up-regulation of c-Jun and c-Fos. These results suggest that the Ras/MAPK/AP-1 signal pathway may be involved in genistein-induced G2/M cell cycle arrest in MDA-MB-231 breast cancer cells. 相似文献
69.
Ng WW Keung W Xu YC Ng KF Leung GP Vanhoutte PM Choy PC Man RY 《Molecular and cellular biochemistry》2008,311(1-2):37-44
Soy consumption is associated with a lower risk of atherosclerotic disease in the oriental population. Genistein is a soy
isoflavone bearing estrogenic properties. Previous experiments in our laboratory demonstrated the potentiation of endothelium-independent
relaxation of coronary artery by both estrogen and genistein. The potentiating effects of both estrogen and genistein were
mediated through the cAMP-signaling pathway. We hypothesize that genistein could enhance protein kinase A (PKA) activity in
porcine coronary artery smooth muscle, thereby offering a mechanism for the potentiation of vascular relaxation by genistein.
In our study, a high concentration of genistein (10−4.5 M) significantly increased PKA activity in porcine coronary artery rings. While genistein at 10−5.5 M and forskolin at 10−7 M had no effect on PKA activity, the combination of the two compounds at the prescribed concentrations caused a significant
increase in PKA activity. The increase in PKA activity by genistein was abolished by SQ 22536 (adenylate cyclase blocker),
but not by NF 449 (Gs protein blocker) or ICI 182780 (estrogen receptor antagonist). Our results suggest that the action of
genistein is mediated via adenylate cyclase, but does not appear to involve Gs protein or ICI 182780-sensitive estrogen receptor. 相似文献
70.