3-羟基异黄酮对卵巢癌的防治作用

3-羟基异黄酮(genistein)属于异黄酮化合物,为一弱植物雌激素,在肿瘤的发生、发展阶段存在着多重抑制效应,其抗肿瘤机制为调节雌激素受体、抑制酪氨酸蛋白激酶活性、抑制血管形成、增强抗氧化酶的活性、调节细胞周期、诱导细胞凋亡、抑制拓扑异构酶的活性等,与多种肿瘤的发生低风险有关.3-羟基异黄酮也可作为一种辅助治疗药物,提高肿瘤细胞对放疗的敏感性,增强化疗药物的抗肿瘤作用,降低肿瘤的复发及转移.3-羟基异黄酮抗肿瘤作用机制及其在卵巢癌中的研究.     

染料木黄酮抗肿瘤侵袭与转移研究进展

大豆提取物染料木黄酮（genistein）是异黄酮类化合物，其化学名为5，7，4-三羟基异黄酮，为一种天然的植物雌激素。近年来关于染料木黄酮的动物和体外实验资料都证实它是一种潜在的肿瘤化学预防剂。最近，染料木黄酮抗肿瘤侵袭转移作用成为国内外研究热点，现综述近年来染料木黄酮抗肿瘤侵袭和转移机制的研究进展。[第一段]     

8-羟基脱氧鸟苷与职业接触抗肿瘤药物者健康效应的研究进展

8-羟基脱氧鸟苷是氧化应激引起DNA损伤的主要产物，在一定程度上反映DNA氧化损伤程度。8-羟基脱氧鸟苷的产生、代谢机制与机体疾病、肿瘤的发生密不可分，抗肿瘤药物是一种能引起DNA氧化损伤的有毒化学物质，长期职业接触抗肿瘤药物者存在潜在健康损害。本文通过对8-羟基脱氧鸟苷产生代谢机制、与抗肿瘤药物的内在联系、与机体肿瘤的关系以及职业接触者机体健康效应等进行综述，以期达到早期监测抗肿瘤药物职业接触者健康状况的目的，提供早期预警，巩固肿瘤专科人才的发展。     

染料木黄酮抗辐射研究进展

染料木黄酮的化学名为5,7,4’-三羟基异黄酮,是大豆异黄酮的主要成分及其生物活性基础。近年来大量研究发现,染料木黄酮具有较强的抗氧化活性,可以淬灭辐射诱导的自由基增多和增加抗氧化酶的活性,抑制膜的脂质过氧化;还可通过调节细胞周期、抑制细胞凋亡、调控细胞基因表达等减轻辐射损伤,促进损伤修复,表现出较强的抗辐射作用。     

肿瘤化学预防天然药物——吲哚-3-甲醇研究进展

十字花科蔬菜在酸性条件下的水解产物吲哚-3-甲醇在体内可被代谢为包括其二聚体3,3’-二吲哚甲烷在内的多种代谢产物。离体实验、动物实验和部分临床试验研究表明吲哚-3-甲醇或3,3’-二吲哚甲烷可通过多种生物学和生物化学机制,如诱导Ⅰ相和Ⅱ相代谢酶类干扰包括雌激素在内的致癌物代谢过程、影响与DNA修复相关的蛋白质表达而发挥增强DNA修复作用、诱导G1期细胞周期阻滞和凋亡的发生及对数种核转录因子的调节等,从而发挥抗肿瘤作用或对肿瘤的化学预防效应。     

049 肿瘤化学预防天然药物——吲哚-3-甲醇研究进展

十字花科蔬菜在酸性条件下的水解产物吲哚-3-甲醇在体内可被代谢为包括其二聚体3，3’-二吲哚甲烷在内的多种代谢产物。离体实验、动物实验和部分临床试验研究表明吲哚-3-甲醇或3，3’-二吲哚甲烷可通过多种生物学和生物化学机制，如诱导Ⅰ相和Ⅱ相代谢酶类干扰包括雌激素在内的致癌物代谢过程、影响与DNA修复相关的蛋白质表达而发挥增强DNA修复作用、诱导G1期细胞周期阻滞和凋亡的发生及对数种核转录因子的调节等，从而发挥抗肿瘤作用或对肿瘤的化学预防效应。     

049肿瘤化学预防天然药物——吲哚-3-甲醇研究进展

十字花科蔬菜在酸性条件下的水解产物吲哚-3-甲醇在体内可被代谢为包括其二聚体3,3'-二吲哚甲烷在内的多种代谢产物.离体实验、动物实验和部分临床试验研究表明吲哚-3-甲醇或3,3'-二吲哚甲烷可通过多种生物学和生物化学机制,如诱导Ⅰ相和Ⅱ相代谢酶类干扰包括雌激素在内的致癌物代谢过程、影响与DNA修复相关的蛋白质表达而发挥增强DNA修复作用、诱导G1期细胞周期阻滞和凋亡的发生及对数种核转录因子的调节等,从而发挥抗肿瘤作用或对肿瘤的化学预防效应.     

染料木黄酮抗肿瘤侵袭与转移研究进展

大豆提取物染料木黄酮(genistein)是异黄酮类化合物,其化学名为5,7,4-三羟基异黄酮,为一种天然的植物雌激素.近年来关于染料木黄酮的动物和体外实验资料都证实它是一种潜在的肿瘤化学预防剂.     

大豆异黄酮与乳腺癌关系研究进展

大豆异黄酮是大豆生长过程中形成的次生代谢产物.由于大豆异黄酮与雌激素分子结构相似,在不同的体内激素条件下既可表现为弱雌激素活性(约相当于雌二醇效果的1/102~1/105),又可表现为抗雌激素活性,因此,又称其为女性雌激素水平调节器(SERMs),并被广泛用于预防和治疗女性更年期综合征^[1].同时大豆异黄酮还可减少人氧化DNA损伤,对氧化损伤的血管内皮细胞具有保护作用;也可抑制肿瘤血管生成以及酪氨酸蛋白激酶活活性^[2].根据国际癌症研究中心(IARC)的统计,全世界每年新增100多万女性乳腺癌患者^[3].     

关于吃豆制品的几个误区

误区1:男性喝豆浆会变“娘”豆浆中含有的大豆异黄酮可在体内发挥雌激素的活性,不过,它的活性很弱,只有雌激素活性的1/100000~1/1000。另外,它在体内具有双向调节的作用,也就是说,当体内雌激素水平低时它可以发挥雌激素的活性,当体内雌激索水平高时它可以抑制雌徼素的活性,因此男性喝豆浆不会变“娘”。     

Tomato and soy polyphenols reduce insulin-like growth factor-I-stimulated rat prostate cancer cell proliferation and apoptotic resistance in vitro via inhibition of intracellular signaling pathways involving tyrosine kinase

We examined the ability of polyphenols from tomatoes and soy (genistein, quercetin, kaempferol, biochanin A, daidzein and rutin) to modulate insulin-like growth factor-I (IGF-I)-induced in vitro proliferation and apoptotic resistance in the AT6.3 rat prostate cancer cell line. IGF-I at 50 micro g/L in serum-free medium produced maximum proliferation and minimized apoptosis. Polyphenols exhibited different abilities to modulate IGF-I-induced proliferation, cell cycle progression (flow cytometry) and apoptosis (Annexin V/propidium iodide and terminal deoxynucleotidyltransferase-mediated deoxyuridine 5'-triphosphate nick end labeling). Genistein, quercetin, kaempferol and biochanin A exhibited dose-dependent inhibition of growth with a 50% inhibitory concentration (IC(50)) between 25 and 40 micro mol/L, whereas rutin and daidzein were less potent with an IC(50) of >60 micro mol/L. Genistein and kaempferol potently induced G(2)/M cell cycle arrest. Genistein, quercetin, kaempferol and biochanin A, but not daidzein and rutin, counteracted the antiapoptotic effects of IGF-I. Human prostate epithelial cells grown in growth factor-supplemented medium were also sensitive to growth inhibition by polyphenols. Genistein, biochanin A, quercetin and kaempferol reduced the insulin receptor substrate-1 (IRS-1) content of AT6.3 cells and prevented the down-regulation of IGF-I receptor beta in response to IGF-I binding. IGF-I-stimulated proliferation was dependent on activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and phosphatidylinositide 3-kinase pathways. Western blotting demonstrated that ERK1/2 was constitutively phosphorylated in AT6.3 cells with no change in response to IGF-I, whereas IRS-1 and AKT were rapidly and sensitively phosphorylated after IGF-I stimulation. Several polyphenols suppressed phosphorylation of AKT and ERK1/2, and more potently inhibited IRS-1 tyrosyl phosphorylation after IGF-I exposure. In summary, polyphenols from soy and tomato products may counteract the ability of IGF-I to stimulate proliferation and prevent apoptosis via inhibition of multiple intracellular signaling pathways involving tyrosine kinase activity.     

染料木素的抑菌活性及其机制的研究

目的研究染料木素(genistein)的抑菌活性以及抑菌机制。方法利用杯碟法、扫描电镜与透射电镜、呼吸代谢抑制实验和SDS-PAGE蛋白谱带变化对染料木素的抑菌活性及其作用机制进行研究。结果染料木素具有明显的抑菌活性;扫描电镜观察,染料木素作用金黄色葡萄球菌24h后,表面出现皱缩、囊泡状或不规则突起结构;透射电镜观察,染料木素处理4h后,金黄色葡萄球菌的细胞质开始固缩,14h后有明显的质壁分离现象,并出现空腔,24h后细胞壁和细胞膜破裂,破裂处有胞浆内容物溢出;染料木素主要是抑制金黄色葡萄球菌的三羧酸循环途径;SDS-PAGE蛋白谱带分析结果显示,染料木素可抑制金黄色葡萄球菌的蛋白合成,使其蛋白总量呈下降趋势,尤其是较大分子量的蛋白含量下降显著,其蛋白量减少了90.1%。结论染料木素对金黄色葡萄球菌有较强的抑菌活性,其抑菌机制是通过破坏细菌细胞壁及细胞膜的完整性、抑制细菌的呼吸代谢和抑制蛋白质的合成等多种作用的结果。     

Effects of Soy Isoflavones on Apoptosis Induction and G2-M Arrest in Human Hepatoma Cells Involvement of Caspase-3 Activation,Bcl-2 and Bcl-XL Downregulation,and Cdc2 Kinase Activity

Genistein, biochanin-A, and daidzein, the predominant soy isoflavones, have been reported to lower the risk of cancer, but it is not known whether they protect against human hepatoma cancer. This study was designed to investigate their effects on cell growth, the cell cycle, and apoptosis induction in the human hepatoma cell lines, HepG2, Hep3B, Huh7, PLC, and HA22T. Genistein, biochanin-A, and daidzein inhibited growth of all five lines in a dose-dependent manner. DNA fragmentation studies and the TUNEL assay demonstrated that isoflavones caused tumor cell death by induction of apoptosis. Activation of caspase-3 and cleavage of the caspase-3 substrate, poly(ADP-ribose)polymerase, was seen in hepatoma cells after 24 hours' exposure to isoflavones. In addition, isoflavone cytotoxicity correlated with downregulation of Bcl-2 and Bcl-XL expression. Synergistic effects of the three isoflavones were observed on cell growth inhibition, apoptosis induction, and anti-apoptotic protein expression. Flow cytometry showed that genistein, but not biochanin-A or daidzein, induced progressive and sustained accumulation of hepatoma cancer cells in the G2/M phase as a result of inhibition of Cdc2 kinase activity. Coapplication of caffeine prevented this cell cycle arrest, but not apoptosis, showing that cell cycle arrest was not necessary for apoptosis. Furthermore, the isoflavones combination also had a significant tumor-suppressive effect in nude mice. These results suggest that isoflavones might be promising agents for the treatment of human hepatoma.     

Effects of soy isoflavones on apoptosis induction and G2-M arrest in human hepatoma cells involvement of caspase-3 activation,Bcl-2 and Bcl-XL downregulation,and Cdc2 kinase activity

Genistein, biochanin-A, and daidzein, the predominant soy isoflavones, have been reported to lower the risk of cancer, but it is not known whether they protect against human hepatoma cancer. This study was designed to investigate their effects on cell growth, the cell cycle, and apoptosis induction in the human hepatoma cell lines, HepG2, Hep3B, Huh7, PLC, and HA22T. Genistein, biochanin-A, and daidzein inhibited growth of all five lines in a dose-dependent manner. DNA fragmentation studies and the TUNEL assay demonstrated that isoflavones caused tumor cell death by induction of apoptosis. Activation of caspase-3 and cleavage of the caspase-3 substrate, poly(ADP-ribose)polymerase, was seen in hepatoma cells after 24 hours' exposure to isoflavones. In addition, isoflavone cytotoxicity correlated with downregulation of Bcl-2 and Bcl-XL expression. Synergistic effects of the three isoflavones were observed on cell growth inhibition, apoptosis induction, and anti-apoptotic protein expression. Flow cytometry showed that genistein, but not biochanin-A or daidzein, induced progressive and sustained accumulation of hepatoma cancer cells in the G2/M phase as a result of inhibition of Cdc2 kinase activity. Coapplication of caffeine prevented this cell cycle arrest, but not apoptosis, showing that cell cycle arrest was not necessary for apoptosis. Furthermore, the isoflavones combination also had a significant tumor-suppressive effect in nude mice. These results suggest that isoflavones might be promising agents for the treatment of human hepatoma.     

Soybean isoflavones, genistein and genistin, inhibit rat myoblast proliferation, fusion and myotube protein synthesis.

The isoflavones, genistein and genistin, are cytotoxic in vitro (e.g. , inhibition of cell proliferation), due in part to inhibition of protein tyrosine kinase and DNA topoisomerase activities. Normal cell functions associated with these enzymatic activities could potentially be impaired in animals through ingestion of soybean products. In this study, cultured rat myogenic cells (L8) were used to determine whether genistein or genistin influences myoblast proliferation and fusion, and myotube protein synthesis and degradation. Genistein or genistin was dissolved in dimethylsulfoxide and included in the culture medium at 0, 1, 10 or 100 micromol/L. Myoblast proliferation was measured by methyl-3H-thymidine incorporation over 48 h. Myoblast differentiation was evaluated by the number of nuclei in multinucleated myotubes. Myotube protein synthesis was measured by 2-h 3H-amino acid incorporation into the myosin and total protein pools after acute (2 h) or chronic (24 h) exposure to similar treatments; protein degradation was measured by measuring radioactivity in protein pools following a time course of protein breakdown after myotube proteins were prelabeled with 3H-amino acids. Genistein or genistin strongly inhibited in vitro myoblast proliferation (P < 0.001) and fusion (P < 0.001) in a dose-dependent manner with effective genistein concentration as low as 1 micromol/L. Genistein or genistin inhibited protein accretion in myotubes (P < 0.001). Decreased protein accretion is largely a result of inhibition on cellular (myofibrillar) protein synthesis rate. No adverse effect on protein degradation was observed. Results suggest that if sufficient circulating concentrations are reached in tissues of animals consuming soy products, genistein/genistin can potentially affect normal muscle growth and development.     

三羟异黄酮保护内毒素诱导急性肺损伤实验研究

目的探讨三羟异黄酮对内毒素(LPS)诱导急性肺损伤(ALI)的保护作用及作用机制。方法将32只大鼠随机分为4组(每组8只):生理盐水组(S组)、三羟异黄酮组(G组)、LPS组(L组)和三羟异黄酮预处理组(G L组)。LPS刺激后,观察6 h。以肺湿干重比(W/D)和支气管肺泡灌洗液(BALF)蛋白含量作为肺损伤的指标。通过检测髓过氧化物酶(MPO)活性及BALF中细胞学分析来评估中性粒细胞的聚集和活性。采用RT-PCR,检测ICAM-1mRNA在肺组织表达的变化。肺组织经HE染色后,观察组织病理学上的改变。结果L组大鼠BALF总蛋白和W/D都较对照组明显升高(P<0.01);同S组比较,在G L组LPS导致了BALF、肺组织匀浆MPO活性及BALF中PMN数目显著增加(P<0.01);L组大鼠肺组织中ICAM-1mRNA表达水平显著高于S组(P<0.01)。预先给予三羟异黄酮可以非常显著抑制LPS引起这些指标的改变(P<0.05或0.01)。三羟异黄酮预处理也改善了LPS所致肺组织形态学上严重的损伤。上述所有参数在G组与S组间差异无统计学意义。结论三羟异黄酮预处理能够减轻LPS诱导的大鼠急性肺损伤。这种效果可能与其下调ICAM-1的表达而抑制PMN在肺组织的聚集、激活有关。     

Genistein induces glucose-regulated protein 78 in mammary tumor cells

Preliminary studies have shown that genistein modulates the expression of some heat shock proteins in mammary tumor cells. In this study, we investigated the effect of genistein pretreatment on the expression of glucose-regulated protein 78 (GRP78) in both estrogen receptor-positive (MCF-7) and -negative (MDA-MB-231) cells. Genistein increased the expression of GRP78 in a dose- and time-dependent manner and suppressed glucose uptake in both cell lines. However, induction of GRP78 by genistein appears not to be directly associated with inhibition of glucose uptake. Genistein treatment also made MDA-MB-231 cells more sensitive to doxorubicin, probably via increased GRP78 expression, but had no effect or even decreased drug sensitivity in MCF-7 cells. These results suggest that genistein may be exploited as an enhancer of chemotherapeutic agents in certain types of breast cancer.     

大豆异黄酮和玉米赤霉烯酮对卵巢癌细胞株PEO4增殖的影响

目的 通过观察大豆异黄酮(genistein,GS)和玉米赤霉烯酮(zearalenone,ZEA)对卵巢癌细胞(PEO4)增殖的影响探讨其雌激素效应。方法 雌激素受体阳性卵巢癌细胞株PEO4在达克尔培养基(DMEM,含小牛血清10％)中采用开放式单层贴壁培养,于加受试物5d前将细胞用磷酸盐缓冲液(PBS)洗涤后改在无酚红高糖DMEM(含活性碳-葡聚糖苷处理过的胎牛血清5％)中培养,实验设溶剂对照、雌激素对照、抗雌激素对照和2种受试物各4个剂量组,采用噻唑蓝法、^3H—TdR掺人法及流式细胞术对PEO4细胞的增殖情况进行分析。结果 与溶剂对照组相比较,96μmol/L对PEO4处理24h,可明显抑制PEO4细胞增殖和细胞DNA合成,并将细胞周期阻滞在G2／M;随着培养时间延长至48h,32μmol/L GS也能明显抑制PEO4细胞增殖,在浓度低于8μmol/L时,GS有促进细胞增殖的趋势。ZEA对PEO4增殖的影响与雌二醇类似,96nmol/L ZEA对细胞处理24h可明显促进PEO4细胞增殖和细胞DNA合成,并将细胞周期由G0／Gl向S期推进,提高细胞分裂增殖指数。结论 ZEA具有较强的雌激素效应,在较低的浓度条件下(8nmol/L,92h)即可促进雌激素受体阳性细胞PEO4的增殖作用;GS对PEO4细胞的影响作用比较复杂,较低浓度的GS(＜10nmol／L)促进细胞的增殖作用,而在高浓度的处理条件下则抑制细胞的增殖作用。这些资料提示高剂量的GS有抗卵巢癌的作用,而ZEA具有雌激素样效应。     

Effects of Genistein on Common Kidney Diseases

Genistein is a naturally occurring phytoestrogen (soy or soybean products) that is classified as an isoflavone, and its structure is similar to that of endogenous estrogens; therefore, genistein can exert an estrogen-like effect via estrogen receptors. Additionally, genistein is a tyrosine kinase inhibitor, which enables it to block abnormal cell growth and proliferation signals through the inhibition of tyrosine kinase. Genistein is also an angiogenesis inhibitor and an antioxidant. Genistein has effects on kidney cells, some of the kidney’s physiological functions, and a variety of kidney diseases. First, genistein exerts a protective effect on normal cells by reducing the inflammatory response, inhibiting apoptosis, inhibiting oxidative stress, inhibiting remodeling, etc., but after cell injury, the protective effect of genistein decreases or even has the opposite effect. Second, genistein can regulate renin intake to maintain blood pressure balance, regulate calcium uptake to regulate Ca²⁺ and Pi balances, and reduce vasodilation to promote diuresis. Third, genistein has beneficial effects on a variety of kidney diseases (including acute kidney disease, kidney cancer, and different chronic kidney diseases), such as reducing symptoms, delaying disease progression, and improving prognosis. Therefore, this paper reviews animal and human studies on the protective effects of genistein on the kidney in vivo and in vitro to provide a reference for clinical research in the future.