二甲基次胂酸促小鼠皮肤肿瘤发生与诱发氧化应激

目的研究二甲基次胂酸对小鼠皮肤促肿瘤发生与诱发氧化应激之间的关系。方法利用7,12二甲基苯并蒽(DMBA)作为始动剂,无机砷主要甲基化代谢产物DMA(V)进一步还原代谢生成的二甲基次胂酸[DMA(Ⅲ)]作为促进剂的致小鼠皮肤肿瘤两阶段动物模型;观察肿瘤的发生数,通过高效液相色谱法(HPLC),测量小鼠皮肤中DNA氧化损伤的生物标志物8-氧-2′-脱氧鸟嘌呤核苷(8-oxodG)的变化。结果在致小鼠皮肤肿瘤动物模型中,背部皮肤局部连续涂抹DMA(Ⅲ),观察到皮肤肿瘤数及表皮组织8-oxodG的生成量明显增多(P<0.05)。结论无机砷甲基化代谢产物的促肿瘤发生作用与DMA(V)在体内进一步还原代谢生成的代谢产物DMA(Ⅲ)诱发的氧化应激密切相关。     

反,反-2,4-癸二烯醛致小鼠DNA氧化损伤作用

目的 探讨反,反-2,4-癸二烯醛(t,t-2,4-DDE)对小鼠DNA氧化损伤作用.方法 ICR雌性小鼠腹腔注射染毒,用高效液相色谱-紫外检测器(HPLC-UV)测定小鼠血清中DNA氧化损伤标志物8-羟基脱氧鸟苷(8-oxodG)含量.结果 t,t-2,4-DDE在1,10,50 mg/kg剂量,染毒小鼠后第10 d,血清中8-oxodG含量随剂量增加而升高,呈剂量-反应关系(P<0.05).50 mg/kg t,t-2,4-DDE剂量染毒后2,6,10 d内,小鼠血清中8-ox-odG浓度随时间延长而升高,呈明显的时间-效应关系(P<0.01).结论 t,t-2,4-DDE是致小鼠DNA氧化-损伤的可疑物质.     

海参硫酸软骨素抑制小鼠Lewis肺癌生长和转移作用的研究

目的探讨海参硫酸软骨素(sea cucumber chondroitin sulfate,SC-CHS)对小鼠肿瘤生长和转移的抑制作用及其机制。方法建立C57 BL/6J小鼠Lewis肺癌自发性肺转移模型,连续腹腔注射给药21 d,剥离原位肿瘤和双侧肺,分别称瘤重和计数肺表面转移灶结节数;分离血清,ELISA法检测小鼠血清中肿瘤坏死因子-α(tumornecrosis factor-α,TNF-α)和γ-干扰素(γ-interferon,γ-IFN)的含量;采用RT-PCR法检测肿瘤组织中缺氧诱导因子(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、乙酰肝素酶(heparanase,Hpa)mRNA的表达。结果 SC-CHS可以显著抑制荷瘤小鼠肿瘤的生长,其平均抑制率为31.5%,并可以显著减少肺表面转移灶结节数(P<0.01),平均抑制率为42.3%;SC-CHS可以显著提高血清中TNF-α和γ-IFN的含量(P<0.05),降低荷瘤小鼠肿瘤组织中HIF-1α、VEGF、Hpa mRNA的表达(P<0.05)。结论 SC-CHS能显著抑制肿瘤细胞在小鼠体内的生长和转移,其机制可能与抑制肿瘤血管新生,提高机体免疫力有关。     

2,2’,4,4’-四溴联苯醚对SH-SY5Y细胞氧化应激与DNA损伤的影响

目的探讨2,2’,4,4’-四溴联苯醚(PBDE-47)对人神经母细胞瘤细胞株(SH-SY5Y)氧化应激的影响和DNA损伤作用。方法用含10%胎牛血清的DMEM培养基在37℃、5%CO2条件下培养SH-SY5Y细胞。当培养细胞处于对数生长期时,用1、2、4、6、8和10μg/mlPBDE-47进行染毒,24h后检测细胞存活率、细胞外乳酸脱氢酶(LDH)漏出率、超氧化物歧化酶(SOD)活性、还原型谷胱甘肽(GSH)和丙二醛(MDA)含量,以及DNA损伤情况。结果与对照组相比,1μg/ml和2μg/ml剂量组细胞存活率略有上升(P<0.05),4、6、8和10μg/ml剂量组细胞存活率显著降低(P<0.05);各染毒剂量组GSH含量显著下降(P<0.05)、尾矩显著上升(P<0.05);4、8和10μg/ml剂量组MDA含量明显高于对照组(P<0.05);4、6、8和10μg/ml剂量组LDH漏出率显著高于对照组(P<0.05)、SOD活力明显低于对照组(P<0.05);6、8和10μg/ml剂量组尾部DNA百分率与对照组比较存在差异的显著性(P<0.05)。结论PBDE-47可引起SH-SY5Y细胞氧化应激和DNA损伤,氧化应激可能在PBDE-47致DNA损伤中起重要作用。     

天然β-胡萝卜素拮抗化学致癌物致突变性

目的观察天然β-胡萝卜素对化学致癌物致突变性的拮抗作用。方法选用改进的体外哺乳类细胞(V79／HGPRT)基因突变试验、改进的小鼠骨髓细胞微核试验和小鼠睾丸染色体畸变试验。结果在V79／HGPRT基因突变试验中天然β-胡萝卜素可抑制AFB1( S9)和丝裂霉素C(-S9)对V79细胞的致突变作用；在体内试验中天然β-胡萝卜素对环磷酰胺诱发的小鼠骨髓细胞微核发生和丝裂霉素C诱发的小鼠睾丸染色体畸变均有明显的抑制作用。结论天然β-胡萝卜素对化学致癌物致突变性有明显的拮抗效果，可用于肿瘤防治。     

大豆染料木素抑制小鼠结肠肿瘤发生过程中PPAR-γ的作用和机制

目的研究染料木素(Genistein)抑制小鼠结肠肿瘤发生过程中,过氧化物酶增殖物激活受体(PPAR-γ的作用和机制。方法用DSS/AOM法诱导雌性KM小鼠结肠肿瘤发生,小鼠共30只,分成正常对照组(normal,N)、结肠肿瘤诱导组(DSS/AOM)和日粮+Genistein(450mg/kg)的结肠肿瘤诱导组(DSS/AOM+Gen)三组,每组10只。分析小鼠结肠肿瘤的发生情况和健康状况,用Western-blot测定小鼠结肠组织相关蛋白的表达变化。结果 Genistein的添加明显降低了小鼠结肠肿瘤发生率,改善了结肠组织结构。结肠肿瘤小鼠PPARγ及PAT家族蛋白,包括Perilipin、TIP-47和ADRP等蛋白的表达显著提高,肿瘤抑制因子FOXO3a蛋白的表达显著降低(P0.05),Genistein的添加对上述蛋白的表达起到了显著的逆转作用(P0.05)。结论 PPARγ蛋白在结肠肿瘤中过表达,而Genistein的添加,抑制了其表达,从而进一步抑制了PAT家族蛋白的表达,使LDs积累减少,FOXO3a蛋白的表达活性升高,最终抑制结肠肿瘤的发生发展。[营养学报,2019,41(2):178-182]     

ω-3 PUFA通过抑制DPD和TS促进5-FU抗SW480移植瘤的作用

目的研究ω-3多不饱和脂肪酸(ω-3 PUFA)联合5-氟尿嘧啶(5-FU)对SW480移植瘤的抑制作用以及对二氢嘧啶脱氢酶(DPD)、胸苷酸合成酶(TS)蛋白表达的影响。方法用BALB/C nu/nu裸小鼠建立SW480移植瘤模型,随机分成4个组(每组8只),并给予含有不同比例ω-3 PUFA的饲料:基础饲料组(总脂肪5%,含ω-3 PUFA 0.3%)、ω-3对照组(总脂肪20%,含ω-3PUFA 0.3%)、低ω-3组(总脂肪20%,含ω-3 PUFA 2.9%)和高ω-3组(总脂肪20%,含ω-3 PU-FA 4.8%),每3 d给予35 mg/kg的5-FU注射,饲养21 d,测定肿瘤重量,采用气相色谱法测定裸小鼠血清中ω-3 PUFA含量,并用蛋白印迹法(Western Blot)检测肝脏DPD、肿瘤TS蛋白表达量。结果移植肿瘤块后,32只裸小鼠一般情况良好且建模成功。ω-3对照组、低ω-3组和高ω-3组的肿瘤重量分别为(0.73±0.15)、(0.51±0.15)、(0.36±0.17)g,高ω-3组低于ω-3对照组(P<0.01);高ω-3和低ω-3组裸小鼠血清中的的ω-3 PUFA含量分别为17.13%、12.26%,均高于ω-3对照组(3.10%)(均P<0.01);高ω-3组、低ω-3组DPD相对表达量分别为0.19、0.61,均低于ω-3对照组(表达量为1)(P<0.05,P<0.01);随着饲料中ω-3 PUFA含量的增加,肿瘤重量下降(R2=0.53)、血清中ω-3 PUFA升高(R2=0.79)、肝脏中DPD的表达降低(R2=0.71)(均P<0.01)。高ω-3组和低ω-3组的游离型TS表达量分别为0.40、0.36,均比ω-3对照组(表达量为1)低,结合型TS表达量分别为0.42、0.25,亦低于ω-3对照组(均P<0.01)。结论ω-3 PUFA可能通过抑制肝细胞DPD和肿瘤细胞TS蛋白的表达来促进5-FU抗结直肠癌的作用。     

1,25-(OH)_2D_3抑制人卵巢癌细胞SKOV-3增殖与调控microRNA-22的表达有关北大核心CSCD

目的通过观察1,25-(OH)2D3对SKOV-3细胞增殖和microRNA-22和microRNA-21表达的影响,探讨microRNAs在1,25-(OH)2D3抗肿瘤增殖中的作用。方法以不同浓度1,25-(OH)2D3(10-9、10-8、10-7mol/L)处理SKOV-3细胞,CCK-8法检测细胞增殖率,real time RT-PCR分析microRNA-22和microRNA-21的表达,流式细胞仪分析细胞周期,TUNEL法检测细胞凋亡。结果 1,25-(OH)2D3对SKOV-3细胞增殖有明显的抑制作用,并且存在着时间剂量依赖关系(P<0.01)。1,25-(OH)2D3可以降低microRNA-22的表达水平(P<0.05),但是不影响microRNA-21的表达。细胞周期分析显示,1,25-(OH)2D3可以诱导SKOV-3细胞阻滞于G0/G1,浓度越高阻滞越明显(P<0.05)。1,25-(OH)2D3促进SKOV-3细胞核内DNA断裂点增加,细胞凋亡增加(P<0.05)。结论在SKOV-3细胞中,1,25-(OH)2D3可能是通过抑制microRNA-22,促进细胞凋亡,调节细胞周期,抑制细胞增殖,从而到达抑制肿瘤的作用。[营养学报,2014,36(1):35-39]     

Treg抑制DC活性调控小鼠肺部炎症发生发展

目的探讨调节性T细胞(Treg)在变态反应性肺泡炎中的作用及Treg对变态反应性肺泡炎发生发展过程中树突状细胞(DC)活性影响。方法腹腔注射抗CD25单克隆抗体建立小鼠Treg消除模型,通过气管灌注1-3-β葡聚糖建立小鼠变态反应性肺泡炎模型,采用流式细胞术检测小鼠肺门淋巴结中树突状细胞活性;苏木素-伊红染色进行病理观察,比较各组小鼠肺组织切片中炎症反应和肉芽肿程度。结果与葡聚糖模型组小鼠比较,Treg消除小鼠肺门淋巴结中CD4+CD25+Treg百分比[(6.76±1.0)%]明显降低(P0.05);组织病理观察显示,Treg消除小鼠肺组织局部炎症反应程度明显重于葡聚糖模型组小鼠;流式细胞术检测发现,葡聚糖灌注后早期,小鼠肺门淋巴结中CD80+MHCII+DC的比例较对照组明显增加;Treg消除小鼠肺门淋巴结和脾细胞中CD80+M HCII+DC比例[(37.3±5.8)%]较葡聚糖模型组小鼠[(24.3±1.9)%]显著升高,差异具有统计学意义(P0.05)。结论 Treg参与抑制变态反应性肺泡炎的发生发展,其机制可能与抑制DC活性发挥免疫抑制作用有关。     

1,3-β-葡聚糖可激活自噬诱发小鼠肺组织炎症

目的 探讨1,3-β-葡聚糖诱导炎症小鼠的肺组织自噬水平，为肺组织炎症的预防、诊断及治疗提供依据。方法 将20只实验小鼠分为两组，1,3-β-葡聚糖实验组、生理盐水对照组，每组10只。小鼠非暴露气管灌注1,3-β-葡聚糖，于灌注后第3天、第28天分别收集小鼠肺组织。采用苏木素伊红和Masson染色，观察肺组织病理改变；采用Western blot检测小鼠体内自噬特异性蛋白微管相关蛋白1轻链3(LC3)和自噬相关蛋白sequestosome 1(p62)的表达水平。结果 镜下可见，与对照组相比，实验组小鼠肺组织出现大量炎症细胞和胶原沉积。Western blot结果显示，实验组小鼠体内LC3-Ⅱ表达水平较对照组升高（t=-2.932,P<0.05）,p62表达水平较对照组升高（t=-5.151,P<0.05）。结论 1,3-β-葡聚糖可明显著提高小鼠肺组织自噬特异性蛋白LC3及自噬相关蛋白p62的表达水平，证明肺组织炎症的小鼠细胞自噬水平升高。     

Effects of Epigallocatechin Gallate,L-Ascorbic Acid, α-Tocopherol,and Dihydrolipoic Acid on the Formation of Deoxyguanosine Adducts Derived From Lipid Peroxidation

Oxidation of polyunsaturated fatty acids (PUFAs) releases α,β-unsaturated aldehydes that modify deoxyguanosine (dG) to form cyclic 1,N ²-propanodeoxyguanosine adducts. One of the major adducts detected in vivo is acrolein (Acr)-derived 1,N ²-propanodeoxyguanosine (Acr-dG). We used a chemical model system to examine the effects of 4 antioxidants known to inhibit fatty acid oxidation on the formation of Acr-dG and 8-oxodeoxyguaonsine (8-oxodG) from the PUFA docosahexaenoic acid (DHA) under oxidative conditions. We found that epigallocatechin gallate (EGCG) and dihydrolipoic acid (DHLA) inhibit both Acr-dG and 8-oxodG formation. In contrast, ascorbic acid and α-tocopherol actually increase Acr-dG at high concentrations and do not show a concentration-dependant inhibition of 8-oxodG. We also studied their effects on blocking Acr-dG formation directly from Acr. EGCG and DHLA can both effectively block Acr-dG formation, but ascorbic acid and α-tocopherol show weak or little effect. These results highlight the complexity of antioxidant mechanisms and also reveal that EGCG and DHLA are effective at suppressing lipid peroxidation-induced Acr-dG and 8-oxodG formation as well as blocking the reaction of dG with Acr.     

表没食子儿茶素没食子酸酯抗突变的实验研究

目的 研究表没食子儿茶素没食子酸酯（ＥＧＣＧ）抗突变作用。方法 以昆明纯种小鼠的骨髓细胞为实验材料,用公认的诱变剂环磷酰胺（ＣＰ）诱发的微核（ＭＮ）率和姐妹杂色单体互换（ＳＣＥ）频率为指标,研究ＥＧＣＧ对ＣＰ诱导小鼠骨髓细胞ＭＮ和ＳＣＥ的影响。结果 ＥＧＣＧ对ＭＮ和ＳＣＥ均具明显抑制作用。结论 ＥＧＣＧ具有抗突变性和潜在的预防肿瘤的作用。     

EGCG对体外应激海马神经元的保护作用及其机制探讨

目的观察表没食子儿茶素没食子酸酯(EGCG)对体外应激海马神经元的保护作用,并探讨其相关作用机制。方法体外培养新生大鼠海马神经元,于原代培养D13时加入不同浓度的皮质酮,采用CCK8(cell counting kit-8)法检测对神经元存活率的影响;加入EGCG(0、0.1、1、5、10μmol/L)预处理24h后,加入皮质酮(CORT,1×10-5mol/L)建立应激损伤模型,采用CCK8法检测神经元的存活率;然后加入LY294002(PI3K/AKT特异性阻断剂)和U012(6ERK1/2特异性阻断剂),检测细胞存活率的改变,并以Hoechst33342核染色法检测细胞凋亡情况。结果皮质酮在10-6～10-4mol/L范围内对海马神经元的神经毒性作用呈现浓度-时间依赖性;0.1μmol/L EGCG处理对皮质酮造成的海马神经元损伤具有保护作用,能够增加细胞存活率,降低细胞凋亡的发生;而加入信号通路阻断剂LY294002(10 mol/L)和U0126(10 mol/L)后,此保护作用受到抑制,其能抑制EGCG对抗CORT引起的神经元细胞存活率下降,细胞凋亡增多。结论 EGCG处理对皮质酮造成的大鼠海马神经元损伤具有保护作用,其作用机制可能与EGCG调控PI3K/AKT、ERK1/2信号转导通路相关。     

Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro

Prostate cancer is an important public health problem in the United States. Seven phytoestrogens found in common herbal products were screened for estrogen receptor binding and growth inhibition of androgen-insensitive (PC-3) and androgen-sensitive (LNCaP) human prostate tumor cells. In a competitive 3H-estradiol ligand binding assay using mouse uterine cytosol, 2.5 M quercetin, baicalein, genistein, epigallocatechin gallate (EGCG), and curcumin displaced > 85% of estradiol binding, whereas apigenin and resveratrol displaced > 40%. From growth inhibition studies in LNCaP cells, apigenin and curcumin were the most potent inhibitors of cell growth, and EGCG and baicalein were the least potent. In PC-3 cells, curcumin was the most potent inhibitor of cell growth, and EGCG was the least potent. In both cell lines, significant arrest of the cell cycle in S phase was induced by resveratrol and EGCG and in G2M phase by quercetin, baicalein, apigenin, genistein, and curcumin. Induction of apoptosis was induced by all of the 7 compounds in the 2 cell lines as shown by TUNEL and DNA fragmentation assays. Androgen responsiveness of the cell lines did not correlate with cellular response to the phytoestrogens. In conclusion, these 7 phytoestrogens, through different mechanisms, are effective inhibitors of prostate tumor cell growth.     

Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer Chemopreventive Polyphenol in Green Tea

Green tea is a popular drink consumed daily by millions of people around the world. Previous studies have shown that some polyphenol compounds from green tea possess anticancer activities. However, systemic evaluation was limited. In this study, we determined the cancer chemopreventive potentials of 10 representative polyphenols (caffeic acid, CA; gallic acid, GA; catechin, C; epicatechin, EC; gallocatechin, GC; catechin gallate, CG; gallocatechin gallate, GCG; epicatechin gallate, ECG; epigallocatechin, EGC; and epigallocatechin gallate, EGCG), and explored their structure-activity relationship. The effect of the 10 polyphenol compounds on the proliferation of HCT-116 and SW-480 human colorectal cancer cells was evaluated using an MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with propidium iodide (PI)/RNase or annexin V/PI. Among the 10 polyphenols, EGCG showed the most potent antiproliferative effects, and significantly induced cell cycle arrest in the G1 phase and cell apoptosis. When the relationship between chemical structure and anticancer activity was examined, C and EC did not show antiproliferative effects, and GA showed some antiproliferative effects. When C and EC esterified with GA to produce CG and ECG, the antiproliferative effects were increased significantly. A similar relationship was found between EGC and EGCG. The gallic acid group significantly enhanced catechin’s anticancer potential. This property could be utilized in future semi-synthesis of flavonoid derivatives to develop novel anticancer agents.     

Anticarcinogenic effects of (-)-epigallocatechin gallate.

BACKGROUND. Our research objective is to develop nontoxic cancer chemopreventive agents and to apply these agents in treating humans. We are identifying agents that inhibit the process of tumor promotion in two-stage carcinogenesis experiments on mouse skin. METHODS. We review (a) the inhibitory effect of penta-O-galloyl-beta-D-glucose (5GG) on tumor promotion by teleocidin, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (5GG is structurally similar to (-)-epigallocatechin gallate (EGCG) and is isolated from hydrolyzed tannic acid); (b) the inhibitory effects of EGCG, the main constituent of Japanese green tea, on tumor promotion with two tumor promoters, teleocidin and okadaic acid, a non-TPA-type tumor promoter; (c) the mechanisms of action of EGCG, a single application of which reduced the specific binding of [3H]TPA and [3H]okadaic acid to a particulate fraction of mouse skin; and (d) the anticarcinogenic effects of EGCG on duodenal carcinogenesis induced by N-ethyl-N'-nitro-N-nitrosoguanidine in male C57BL/6 mice. EGCG is a nontoxic compound. CONCLUSION. We believe that the main constituent of Japanese green tea, EGCG, is a practical cancer chemopreventive agent available in everyday life.     

Epigallocatechin gallate attenuates fibrosis,oxidative stress,and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD,PI3 K/Akt/FoxO1, and NF-kappa B pathways

Purpose

To investigate the protective mechanisms of an 85 % pure extract of (?) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD).

Methods

Female Sprague–Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses.

Results

Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats.

Conclusions

Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.     

Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells

We previously demonstrated that 50% of (-)-epigallocatechin gallate (EGCG) was present in methylated form (4″-MeEGCG) in human prostate tissue, which is less bioactive. We therefore investigated whether quercetin, a natural inhibitor of catechol-O-methyl transferase (COMT), will inhibit EGCG methylation leading to enhanced antiproliferative activity of EGCG in prostate cancer cells. Incubation with both quercetin and EGCG for 2 h increased the cellular concentrations of EGCG by 4- to 8-fold and 6- to 10-fold in androgen-independent PC-3 cells and androgen-dependent LNCaP cells, respectively. Concurrently, the percent of 4″-MeEGCG in the total EGCG was decreased from 39% to 15% in PC-3 cells and from 61% to 38% in LNCaP cells. Quercetin and EGCG in combination synergistically inhibited cell proliferation, caused cell cycle arrest, and induced apoptosis in PC-3 cells. In LNCaP cells, EGCG and quercetin exhibited a stronger antiproliferative activity leading to an additive effect. The synergistic effect of these 2 agents in PC-3 cells could be based on the fact that EGCG primarily inhibited COMT activity, whereas quercetin reduced the amount of COMT protein. In summary, quercetin combined with EGCG in vitro demonstrated enhanced inhibition of cell proliferation by increasing the intracellular concentration of EGCG and decreasing EGCG methylation.     

Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 production

Epidemiological and animal studies have indicated that consumption of green tea and high vitamin E intake are associated with a reduced risk of developing certain forms of cancer. However, the inhibitory mechanism of green tea catechins and vitamin E in angiogenesis, an important process in tumor growth, has not been well established. In the present study, alpha-tocopherol and several major catechins of green tea (catechin, epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate) were tested for their ability to inhibit tube formation in vitro using a model in which human microvascular endothelial cells were exposed to a constant rate of a physiologically low level of H2O2. In this model, the production of interleukin (IL)-8 by human microvascular endothelial cells at a low level of H2O2 was required for angiogenesis, as assessed by tube formation in three-dimensional gel in culture. Vitamin E (d-alpha-tocopherol, 40 microM) in the culture media significantly reduced IL-8 production and angiogenesis. Among the green tea catechins, epigallocatechin (0.5-1 microM) was the most effective in reducing IL-8 production and inhibiting angiogenesis. These results suggest that consumption of green tea catechins or supplemental intake of vitamin E may have preventive effects on tumor development, mediated, at least in part, through inhibition of angiogenesis via suppression of IL-8 production.