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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isoflavonoids are natural plant compounds and possess antitumorigenic properties. Many environmental chemicals have been found to be estrogenic and can enhance tumor growth in estrogen receptor-positive cells. In the present study, the effects of genistein, daidzein, biochanin A, formononetin, and equol on the proliferation of estrogen receptor-positive MCF-7 cells induced by synthetic chemicals 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), 4-nonylphenol (4-NP), and 5-octylphenol (5-OP) found in the environment were investigated. Genistein, biochanin A, equol, and to some extent daidzein, but not formononetin, at < 10 microM can enhance the growth of MCF-7 cells in the absence of environmental chemicals. Formononetin was toxic to MCF-7 cells at the tested concentrations. The environmental chemicals 4-NP, 5-OP, and o,p'-DDT and the natural estrogen 17 beta-estradiol at 5, 5, and 10 microM and 5 nM, respectively, induced proliferation of MCF-7 cells. In the presence of isoflavonoids (> 25 microM), the environmental chemical-induced cell proliferation was inhibited. Individually, genistein (IC50 = 25-33 microM) was the most potent inhibitor against the induced proliferation of MCF-7 cells of the isoflavonoids needed for a 50% suppression of growth induced by 4-NP, 5-OP, and o,p'-DDT. A mixture of isoflavonoids was the most potent inhibitor against the induced proliferation. Estrogen receptor-dependent and -independent pathways could be involved in the inhibitory actions of isoflavonids. Because it is impossible to have a chemical-free environment, the in vitro data presented here are of practical importance to develop evolving dietary strategies and tactics against the adverse health effects of environmental chemicals.
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PMID:Effect of soy-derived isoflavonoids on the induced growth of MCF-7 cells by estrogenic environmental chemicals. 963 96

Dietary genistein, a natural flavone compound found in soy, has been proposed to be responsible for the low rate of breast cancer in Asian women. The cellular mechanisms of genistein's chemopreventive effects in vio have been largely unexplored. In our previous studies, we found that genistein exerted pronounced antiproliferative effects on both estrogen receptor-positive and -negative human breast carcinoma cells through G2-M arrest, induction of p21WAF1/CIP1 expression, and apoptosis. Because chemopreventive effects need not be limited to antiproliferation, we decided to examine whether genistein exerted other suppressive effects on breast carcinoma progression. Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1. These in vitro and in vivo studies demonstrate that genistein exerts multiple suppressive effects on breast carcinoma cells, suggesting that its mechanism of chemoprevention is pleiotropic.
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PMID:Genistein exerts multiple suppressive effects on human breast carcinoma cells. 980 90

The studies presented were conducted to assess the effect of the soy isoflavone genistein on proliferation of estrogen-independent human breast cancer cells (MDA-MB-231) in vitro and in vivo. Genistein (20 mcmol/L) inhibited cell proliferation in vitro by approximately 50%. Cell cycle progression was blocked in G(2)/M with 40 and 80 mcmol/L genistein. To evaluate the effect of dietary genistein on tumor growth in vivo, genistein was fed to female athymic mice inoculated with MDA-MB-231 cells. After solid tumor masses had formed, mice were fed genistein at a dose (750 mcg/g AIN-93G diet), shown to produce a total plasma genistein concentration of approximately 1 mcmol/L. This dose of genistein did not significantly (P > 0.05) alter tumor growth. Studies were then conducted to assess the effect of dietary genistein on initial tumor development and growth. Genistein (750 mcg/g AIN-93G diet), fed 3 d before cells were inoculated into mice, did not significantly (P > 0.05) inhibit tumor formation or growth. The plasma concentration of genistein in mice fed this dose of dietary genistein (750 mcg/g AIN-93G diet) does not appear sufficient to inhibit tumor formation or growth. Dietary genistein at 750 mcg/g AIN-93G diet does not inhibit tumor formation or growth. Additional studies were conducted to determine the effect of dietary dosages ranging from 0 to 6000 mcg/g AIN-93G diet on plasma genistein concentration. Plasma genistein concentration increased in a dose-dependent manner up to 7 mcmol/L at 6000 mcg/g AIN-93G diet. These data suggest that although genistein inhibits cancer cell growth in vitro, it is unlikely that the plasma concentration required to inhibit cancer cell growth in vivo can be achieved from a dietary dosage of genistein.
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PMID:Genistein inhibits growth of estrogen-independent human breast cancer cells in culture but not in athymic mice. 1086 33

Genistein is a plant isoflavonoid bearing potent tumor growth-regulating characteristics. This effect of genistein has been attributed partially to its tyrosine kinase-regulating properties, resulting in cell-cycle arrest and limited angiogenesis. Genistein has been used in chemotherapy-resistant cases of advanced leukemia with promising results. Here we demonstrate that genistein primarily affects nucleic acid synthesis and glucose oxidation in tumor cells using the [1,2-(13)C2]glucose isotope as the single tracer and gas chromatography/mass spectrometry to follow various intracellular glucose metabolites. The ribose fraction of RNA demonstrated a rapid 4.6%, 16.4%, and 46.3% decrease in isotope uptake through the nonoxidative branch of the pentose cycle and a sharp 4.8%. 24.6%, and 48% decrease in 13CO2 release from glucose after 2, 20, and 200 micromol/L genistein treatment, respectively. Fatty acid synthesis and the 13C enrichment of acetyl units were not significantly affected by genistein treatment. De novo glycogen synthesis from media glucose was not detected in cultured MIA cells. It can be concluded from these studies that genistein controls tumor growth primarily through the regulation of glucose metabolism, specifically targeting glucose carbon incorporation into nucleic acid ribose through the nonoxidative steps of the pentose cycle, which represents a new paradigm for the antiproliferative action of a plant phytochemical.
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PMID:Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. 1113 60

Genistein has been shown to be an inhibitor of tumor growth as well in vitro as in vivo. In addition to its antitumor effect, genistein reveals the antimetastatic and antiangiogenic properties. In this paper we described the results of our studies on the antimetastatic activity of genistein alone or combined with cyclophosphamide (CY) in mice which before this treatment were exposed to surgical excision of the primary tumor. Three transplantable subcutaneously growing mouse tumors were applied: Lewis lung cancer (LL2), B16F-10 melanoma and 16/C mammary cancer. The antitumor and antimetastatic effect was evaluated by the estimation of a number of lung colonies and a number of primary tumor recurrence as compared to the control mice exposed to the s.c. tumor extirpation only. Twenty days after the surgery, an average of 52 lung tumor colonies per mouse were detected in control mice bearing LL2 cancer. The treatment with genistein resulted in the reduction of the lung colonies to 24 per mouse. The treatment with CY reduced the number of lung colonies to 12 (p < 0.05) and combined treatment with both agents to 4 (p < 0.05). The percentage of primary tumor recurrence was 25, 86, 67 and 80% in the control, genistein treated, CY treated, and genistein + CY treated mice, respectively. Twenty days after the surgery, no lung metastases in the control mice bearing B16F-10 melanoma were observed. The percentage of primary tumor recurrence in the control, genistein treated, CY treated and genistein + CY treated mice was: 86, 29, 57 and 67% respectively. Two different protocols of the treatment with genistein were applied in 16/C mammary cancer model. In the first one genistein was injected before and in the other after surgical excision of tumor. The histological examination revealed the presence of lung metastases in all, untreated and treated, according to both protocols groups of mice. The percentage of primary tumor recurrence in the control mice, genistein treated according to the protocol I, and II was: 100, 40, and 40%, respectively.
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PMID:The antitumor effect of postoperative treatment with genistein alone or combined with cyclophosphamide in mice bearing transplantable tumors. 1129 63

We have demonstrated that the isoflavone, genistein, stimulates growth of estrogen-dependent human breast cancer (MCF-7) cells in vivo (C. Y. Hsieh et al., Cancer Res., 58: 3833-3838, 1998). The isoflavones are a group of phytoestrogens that are present in high concentrations in soy. Whether consumption of genistein from soy protein will have similar effects on estrogen-dependent tumor growth as pure genistein has not been investigated in the athymic mouse tumor implant model. Depending on processing, soy protein isolates vary widely in concentrations of genistein. We hypothesize that soy isolates containing different concentrations of genistein will stimulate the growth of estrogen-dependent cells in vivo in a dose-dependent manner. To test this hypothesis we conducted experiments in which these soy protein isolates were fed to athymic mice implanted s.c. with estrogen-dependent tumors. Genistein content (aglycone equivalent) of the soy isolate diets were 15, 150, or 300 ppm. Positive (with 17beta-estradiol pellet implant) and negative (no 17beta-estradiol) control groups received casein-based (isoflavone-free) diets. Tumor size was measured weekly. At completion of the study animals were killed and tumors collected for evaluation of cellular proliferation and estrogen-dependent gene expression. Incorporation of bromodeoxyuridine into cellular DNA was used as an indicator of cell proliferation, and pS2 mRNA was used as an estrogen-responsive gene. Soy protein diets containing varying amounts of genistein increased estrogen-dependent tumor growth in a dose-dependent manner. Cell proliferation was greatest in tumors of animals given estrogen or dietary genistein (150 and 300 ppm). Expression of pS2 was increased in tumors from animals consuming dietary genistein (150 and 300 ppm). Here we present new information that soy protein isolates containing increasing concentrations of genistein stimulate the growth of estrogen-dependent breast cancer cells in vivo in a dose-dependent manner.
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PMID:Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. 1143 39

A variety of health benefits, including protection against breast cancer, have been attributed to soy food consumption, primarily because of the soybean isoflavones (genistein, daidzein, glycitein). Isoflavones are considered to be possible selective estrogen receptor modulators but possess nonhormonal properties that also may contribute to their effects. Concern has arisen over a possible detrimental effect of soy in breast cancer patients because of the estrogen-like effects of isoflavones. Genistein exhibits a biphasic effect on the growth of MCF-7 cells in vitro, stimulating proliferation at low concentrations but inhibiting it at high concentrations. In ovariectomized athymic mice implanted with MCF-7 cells, both genistein and soy protein stimulate tumor growth in a dose-dependent manner. In contrast, in intact mice fed estrogen, genistein inhibits tumor growth. Although two studies in premenopausal women suggested that soy exerts estrogenic-like effects on breast tissue, recently conducted year-long studies indicated that isoflavone supplements do not affect breast tissue density in premenopausal women and may decrease density in postmenopausal women. These latter effects are opposite to those of hormone replacement therapy (HRT). Importantly, substantial data suggest that the progestogen, not the estrogen, component of HRT increases risk of developing breast cancer. Furthermore, recently conducted studies have failed to find that even HRT reduces survival in breast cancer patients. Overall, the data are not impressive that the adult consumption of soy affects the risk of developing breast cancer or that soy consumption affects the survival of breast cancer patients. Consequently, if breast cancer patients enjoy soy products, it seems reasonable for them to continue to use them.
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PMID:Soy for breast cancer survivors: a critical review of the literature. 1169 55

Two principle soy-derived isoflavones, genistein and daidzein, are believed to play a key role in inhibiting tumor growth. The molecular basis of the anti-tumor activity of these two isoflavones has not been fully established. To determine the mechanism of action of the above phytochemicals on estrogen-responsive genes, we tested the effect of the same on the expression of Estrogen-Regulated mRNA Stabilizing Factor (E-RmRNASF). E-RmRNASF is expressed in the liver in response to estrogen, and is responsible for estrogen-mediated stabilization of apolipoprotein II mRNA (Ratnasabapathy, 1995, Cell. Mol. Biol. Res, 41: 583-594). The estrogen-mediated hepatic expression of apolipoprotein II mRNA is regulated transcriptionally, and also post-transcriptionally in part by stabilization of its mRNA. E-RmRNASF protects the RNA from targeted endonucleolytic degradation. The hepatic expression of E-RmRNASF is also modulated by certain estrogenic and antiestrogenic nonsteroidal environmental xenobiotics (Ratnasabapathy et al., 1997, Biochem. Pharmacol., 53: 1425-1434). Roosters were administered estrogen, genistein, or daidzein parenterally and tested for hepatic expression of E-RmRNASF. Expression of E-RmRNASF in the livers was stimulated in roosters who received estrogen and genistein, indicating that they are agonistic at the chicken estrogen receptor. However, a lack of induction of E-RmRNASF expression in the liver was seen with control roosters treated with the vehicle and those treated with daidzein. To determine whether daidzein was anti-estrogenic, roosters were given combinations of estrogen and increasing concentrations of daidzein. Daidzein at concentrations ranging from 5-1000 micromole/kg failed to antagonize stimulation of E-RmRNASF by 5 micromoles/kg estrogen. To determine whether genistein or daidzein exerted partial agonistic effects, roosters were given increasing concentrations of genistein, daidzein or estrogen alone, or combinations of estrogen and increasing doses of genistein or daidzein. At low to intermediate concentrations genistein by itself failed to stimulate E-RmRNASF, and was agonistic only at high concentrations. Genistein at the low concentrations failed to antagonize estrogenic stimulation of E-RmRNASF. At the intermediate concentrations however, genistein blocked stimulation of E-RmRNASF by estrogen, even though by itself could not exert a stimulatory effect. At the higher concentrations genistein stimulated E-RmRNASF regardless of the presence or absence of estrogen. At the higher ratios, the lack of inhibition of estrogenic stimulation by genistein was most likely due to its own agonistic activity. Therefore, genistein appears to behave as a partial agonist; behaves as an agonist by itself, and as an antagonist in the presence of estrogen. However, daidzein did not display any estrogenic or antiestrogenic activity at the concentrations tested.
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PMID:Inhibition of estrogenic stimulation of gene expression by genistein. 1208 84

An IL-10 responsive signal protein, termed IL-10E1, was cloned from human prostate cancer PC-3 ML cells based on its binding affinity for a novel enhancer element (i.e., HTE-1: 5'-CACGATGACTCATCACTGTTGAAAGACA-3') of the Tissue Inhibitor of metalloproteinase-1 (TIMP-1) gene. Electrophoretic mobility shift assays (EMSAs) and enzyme linked immuno-sandwich assays (ELISAs) showed that IL-10 stimulated the rapid translocation of IL-10E1 to the nucleus and the activation of TIMP-1 expression in 4 different androgen dependent primary prostate tumor lines generated in our laboratory (i.e. HPCA-5a, 5b, 5c and 5d lines). IL-10 signaling was blocked by a variety of agents, including IL-10 receptor antibodies, alpha-toxin, and Genistein. The inhibition of IL-10 signaling and IL-10E1 expression correlated directly with a significant decrease in TIMP-1 expression by the HPCA-5a, 5b, 5c and 5d cell lines. Following permanent transfection of HPCA-5a and 5c cells with the IL-10 gene the growth of tumor xenografts in SCID CB17 mice was severely retarded, yielding tiny, poorly vascularized tumors by approximately 90 days post-inoculation s.c. ELISAs showed that these tumors expressed elevated levels of IL-10, IL-10E1 and TIMP-1 compared with tumors from non-transfected or Mock transfected cell lines. We conclude that the IL-10/IL-10 receptor axis (and IL-10E1 signaling) regulation of TIMP-1 expression plays a key role in inhibiting tumor growth, perhaps by blocking tumor vascularization.
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PMID:IL-10/IL-10 receptor signaling regulates TIMP-1 expression in primary human prostate tumor lines. 1249 89

The role of beta-glucuronidase in genistein biotransformation was investigated in a human breast cancer MDA-MB-231 xenogeneic athymic mouse model. Genistein combined polysaccharide (GCP), a genistein aglycone rich functional food supplement was used in these experiments. Tumor-bearing mice were subjected to oral administration of GCP for 28 days. GCP treatment significantly inhibited tumor growth. Induction of apoptosis by GCP treatment was related to activation of cleavage of poly(ADP-ribose)polymerase, induction of the p21 protein expression and reduction of cyclin B1 expression in the tumor tissues. Genistein exists as a glucuronide conjugate in normal organ tissues, and the conjugated genistein lacks the physiological activity of the aglycone. Tumor tissues contain large amounts of beta-glucuronidase, the enzyme that converts the genistein beta-glucuronide conjugate into genistein aglycone. The resulting genistein aglycone exerts its chemopreventive activities, including the induction of apoptosis in tumor tissues, and, finally, leads to tumor growth inhibition.
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PMID:Inhibition of human breast cancer growth by GCP (genistein combined polysaccharide) in xenogeneic athymic mice: involvement of genistein biotransformation by beta-glucuronidase from tumor tissues. 1262 3


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