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1.
B. A. Stoll 《Annals of oncology》1997,8(3):223-225
Background: The study reviews the anticancer properties of naturalisoflavones which occur in especially high concentration in soybeans. Itconsiders the suitability of soybean products for clinical trials aiming toreduce the progression of breast cancer.Methods: Evidence is reviewed that plant isoflavones such asgenistein show cytostatic activity against human mammary cancer cell linesin vitro and can also suppress carcinogen-induced mammary cancer inyoung and mature rats.Results: Plant isoflavones are converted in the bowel to compoundswith potential antioestrogenic and antioxidative properties. These compoundsshow cytostatic activity for both oestrogen receptor-positive and negativehuman mammary cancer cell lines, and also inhibit growth and progress of therat mammary cancer model. The high content of soybean products in the diet ofAsian women has been postulated as one reason for their relatively low breastcancer incidence.Conclusion: Preclinical studies suggest that soybean products begiven priority for clinical trials in breast cancer protection. A pilot studycould test soy protein supplements as long-term adjuvant dietary treatmentafter primary surgery for early breast cancer, looking for a decrease in therisk of recurrence or of second primary tumours. 相似文献
2.
异黄酮对PC-3细胞凋亡的诱导作用 总被引:2,自引:0,他引:2
目的 : 通过观察染料木素 (genistein,GS)、大豆甙元 (daidzein,DA)和黄豆黄素(glycitein,GL)对前列腺癌细胞 (PC- 3 )凋亡的影响 ,探讨通过膳食途径预防前列腺癌发生危险性的可行性。方法 : 将 PC- 3细胞在 RPMI1 6 4 0培养液 (含 1 0 %小牛血清 )中采用开放式单层贴壁培养。实验设溶剂对照及三种受试物各三个剂量组 ,采用流式细胞术 ,DNA凋亡片段凝胶电泳和细胞 HE染色法分析三种常见异黄酮类物质对 PC- 3细胞凋亡的影响。结果 : 与对照组相比 ,流式细胞仪分析结果表明 ,5 0μ mol/L GS、75μ mol/L DA和 75μ mol/L GL对 PC- 3细胞处理 72 h,二倍体细胞 (G1期细胞 )相对减少 ,亚二倍体细胞峰 (即细胞凋亡率 )逐渐增多 ,即凋亡细胞比例逐渐增多 ;DNA凋亡片段凝胶电泳和细胞苏木素染色结果也显示 ,三种受试物能够诱导 PC- 3细胞凋亡 ,且这种作用存在剂量 -效应关系。结论 : 异黄酮类化合物染料木素、大豆甙元和黄豆黄素均具有诱导 PC- 3细胞凋亡的作用 ,这一结果提示 ,该类物质是可通过诱导细胞凋亡而发挥其抗肿瘤作用的。 相似文献
3.
Chen T Hutts RC Mei N Liu X Bishop ME Shelton S Manjanatha MG Aidoo A 《Environmental and molecular mutagenesis》2005,45(5):409-418
A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats. 相似文献
4.
用高效液相色谱法测定了西洋参 DNA导入大豆后代的异黄酮类成分、大豆苷 (daidzin)、大豆黄素(daidzein)、染料木苷 (genistin)、染料木素 (genistein)的含量 ,采用 U nisil Q C1 8柱 ,4.6 mm× 2 5 0 m m,流动相乙腈 - 0 .0 0 3mol/L 磷酸氢二钠 (17∶ 83) ,流速 1.0 m L/min,检测波长 2 5 4nm,结果表明 ,4种成分分离效果好 ,成分含量发生了广泛变异 ,从中可筛选出有效成分含量较高的新材料 相似文献
5.
The chemopreventive properties of soy isoflavonoids in animal models of breast cancer 总被引:8,自引:0,他引:8
Stephen Barnes 《Breast cancer research and treatment》1997,46(2-3):169-179
Genistein (5,7,4-trihydroxyisoflavone), one of two major isoflavonoids in soy, has anti-proliferative effects on mitogen-stimulated cell growth of human breast cancer cells in culture and is a candidate for use in the prevention of breast cancer. Soy protein preparations containing isoflavonoid conjugates have chemopreventive activity in carcinogen-induced rat models of breast cancer. Recent experiments in these models with purified genistein have revealed that the timing of the exposure of rats to this isoflavonoid is critical. Rats treated neonatally or prepuberally with genistein have a longer latency before the appearance of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and a marked reduction in tumor number. The mechanism of genistein's preventive action is in part dependent on its estrogenic activity, which causes a more rapid differentiation of the cells of the mammary gland, analogous to the effects of an early pregnancy. Rats administered genistein after 35 days of age have smaller alterations in breast cancer risk, with a maximum reduction in mammary tumor number of 27%. In ovariectomized nude mice, dietary genistein increases cell proliferation of human breast cancer MCF-7 cell xenografts compared with a control diet. This estrogen-like effect of genistein is not observed in non-ovariectomized rats. Future studies on the anticancer potential of soy isoflavonoids should examine their interaction with other phytochemical components of soybeans and exploit newly developed animal models of breast cancer in which specific genes have been activated or inactivated. 相似文献
6.
- Here we compared the effects of various inhibitors of the activity of protein tyrosine kinase on (i) the expression of the activity of the inducible isoform of nitric oxide (NO) synthase (iNOS) caused by endotoxin (lipopolysaccharide, LPS) in cultured macrophages, (ii) the induction of iNOS and cyclo-oxygenase 2 (COX-2) protein and activity in rats with endotoxaemia, and (iii) the circulatory failure and organ dysfunction caused by LPS in the anaesthetized rat.
- Activation of murine cultured macrophages with LPS (1 μg ml−1) resulted, within 24 h, in a significant increase in nitrite (an indicator of the formation of NO) in the cell supernatant. This increase in nitrite was attenuated by the tyrphostins AG126, AG556, AG490 or AG1641 or by genistein in a dose-dependent fashion (IC50: ∼15 μM). In contrast, tyrphostin A1 (an analogue of tyrphostin AG126) or daidzein (an analogue of genistein) had no effect on the rise in nitrite caused by LPS.
- Administration of LPS (E. coli, 10 mg kg−1, i.v.) caused hypotension and a reduction of the pressor responses elicited by noradrenaline (NA, 1 μg kg−1, i.v.). Pretreatment of rats with the tyrphostins AG126, AG490, AG556, AG1641 or A1 attenuated the circulatory failure caused by LPS. Although genistein attenuated the vascular hyporeactivity to NA, it did not affect the hypotension caused by LPS. Daidzein did not affect the circulatory failure caused by LPS.
- Endotoxaemia for 360 min resulted in rises in the serum levels of (i) urea and creatinine (indicators of renal failure), (ii) alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and γ-glutamyl transferase (γGT) (indicators of liver injury/dysfunction), lipase (an indicator of pancreatic injury) as well as lactate (an indicator of tissue hypoxia). None of the tyrosine kinase inhibitors tested had a significant effect on the rise in the serum levels of urea, but the tyrphostins AG126, AG556 or A1 significantly attenuated the rises in the serum levels of creatinine caused by LPS. In addition, all tyrphostins and genistein attenuated the liver injury/failure, the pancreatic injury, the hypoglycaemia and the lactic acidosis caused by LPS. In contrast, daidzein did not reduce the organ injury/dysfunction or the lactic acidosis caused by LPS.
- Injection of LPS resulted (within 90 min) in a substantial increase in the serum level of tumour necrosis factor α (TNFα), which was attenuated by pretreatment of LPS-rats with any of the tyrphostins used. Genistein, but not daidzein, also reduced the rise in the serum levels of TNFα caused by LPS. Endotoxaemia for 6 h also resulted in a substantial increase in the expression of iNOS and COX-2 protein and activity in the lung, which was attenuated by pretreatment of LPS-rats with the tyrphostins AG126, AG556 or genistein, but not by daidzein.
- Thus, tyrphostins (AG126, AG490, AG556, AG1641 or A1) and genistein, but not daidzein (inactive analogue of genistein), prevent the (i) circulatory failure, (ii) the multiple organ dysfunction (liver and pancreatic dysfunction/injury, lactacidosis, hypoglycaemia), as well as (iii) the induction of iNOS and COX-2 protein and activity in rats with endotoxic shock
7.
Soy-based formulas and phyto-oestrogens: a safety profile 总被引:1,自引:0,他引:1
VL Miniello GE Moro M Tarantino M Natile L Granieri L Armenio 《Acta paediatrica (Oslo, Norway : 1992)》2003,92(S441):93-100
Phyto-oestrogens are non-steroidal plant-derived compounds that possess oestrogenic activity and act as selective oestrogen receptor modulators (SERMs). Among the dietary oestrogens, the isoflavone class enjoy a wide-spread distribution in most of the members of the Leguminosae family, including such prominent high-content representatives as soybean. Phyto-oestrogen research has grown rapidly in recent years owing to epidemiological studies suggesting that diets rich in soy may be associated with potential health benefits. There is a paucity of data on endocrine effects of soy phytochemicals during infancy, the most sensitive period of life for the induction of toxicity. The safety of isoflavones in infant formulas has been questioned recently owing to reports of possible hormonal effects. Infants fed soy formula receive high levels of phyto-oestrogens in the form of isoflavones (genistein, daidzein and their glycosides). To date, no adverse effects of short- or long-term use of soy proteins have been observed in humans and exposure to soy-based infant formulas does not appear to lead to different reproductive outcomes than exposure to cow milk formulas. Soy formula seems to be a safe feeding option for most infants. Nevertheless, much closer studies in experimental animals and human populations exposed to phyto-oestrogen-containing products, and particularly soy-based infant formulas, are necessary. 相似文献
8.
Genistein, tyrphostin and piceatannol, which are specific inhibitors of protein tyrosine kinase, were screened for their effects on the motility of intact and demembranated hamster spermatozoa. Of the three inhibitors only piceatannol inhibited the motility of intact spermatozoa. None of the inhibitors had any inhibitory effect on the reactivation of motility of demembranated hamster spermatozoa. Taken together these results indicated that a protein tyrosine kinase associated with the membrane of hamster spermatozoa was probably involved in sustenance of hamster sperm motility. Therefore in the present study a membrane-associated protein tyrosine kinase was purified from a detergent-soluble extract of plasma membranes of mature hamster spermatozoa. The purification involved cation exchange chromatography on fast protein liquid chromatography (FPLC) followed by affinity chromatography either on an antiphosphotyrosine antibody agarose or poly glu-tyr agarose column. The pure protein tyrosine kinase had an apparent molecular mass of 45 kDa. The enzyme was not inhibited by genistein or herbimycin but was inhibited by piceatannol. This is the first report on the purification of a sperm plasma membrane-associated protein tyrosine kinase, an enzyme which has also been implicated in hamster sperm motility. 相似文献
9.
目的 为保证染料木素临床用药的安全 ,评价其生殖毒性。方法 16,160 ,480 mg/(kg· d)染料木素分别连续 ig雄、雌性大鼠 60 d,14 d后合笼 ,雄性大鼠给药至交配结束 ,雌性大鼠给药至妊娠第 17天 ,观察染料木素对大鼠的受胎能力、生殖系统及子代的影响。结果 染料木素 480 mg/(kg· d)引起亲代雄性大鼠精子活动度下降 ,但未发现睾丸病变 ,也未影响雄鼠生殖能力 ;同时使雌鼠妊娠期体重增长明显低于其他组 (P<0 .0 1) ,但未影响胚胎形成、仔鼠生长发育。 160 mg/(kg· d)剂量对亲代和子代未引起明显的异常。结论 染料木素 160 mg/(kg·d)对雌、雄性大鼠无一般生殖毒性作用 相似文献
10.
染料木黄酮、拟雌内酯及槲皮素对孕烷X受体介导的CYP3A4转录的调节作用 总被引:9,自引:0,他引:9
目的 研究植物雌激素中的染料木黄酮(GST)、拟雌内酯 (COM)及槲皮素 (QU)能否通过活化人孕烷X受体 (PXR)诱导CYP3A4的转录表达。方法用PXR依赖的瞬时转染报告基因试验检测 3种植物雌激素的诱导作用。结果 GST ,COM和QU均能通过活化PXR诱导HepG2 细胞CYP3A4基因的转录表达 ,最大诱导倍数 (相对于用浓度为 0 .1%的DMSO处理的细胞 )在本实验中分别为 11.97(P <0 .0 1) ,2 .98(P <0 .0 1)和 3.2 8(P <0 .0 1)。结论 GST ,COM和QU均能诱导CYP3A4的转录表达 ,其作用机制通过活化PXR。GST ,COM和QU的摄入可能影响其他CYP3A4底物尤其是药物在体内的代谢。 相似文献