表没食子儿茶素没食子酸酯抗肿瘤分子机制

茶多酚及其主要成分表没食子儿茶素没食子酸酯（EGCG）具有明显的抗肿瘤作用,既可通过抑制核转录因子-κB（NF-κB）、丝裂原活化蛋白激酶（MAPK）、表皮生长因子受体、胰岛素样生长因子、环氧合酶（COX）-2等相关信号通路防止肿瘤发生,也可通过抑制血管内皮生长因子、基质金属蛋白酶（MMP）、尿激酶纤溶酶原激活物等途径阻止肿瘤转移,有望成为一种天然的抗肿瘤药物。     

表没食子儿茶素没食子酸酯抗肿瘤分子机制

茶多酚及其主要成分表没食子儿茶素没食子酸酯(EGCG)具有明显的抗肿瘤作用,既可通过抑制核转录因子-κB(NF-κB)、丝裂原活化蛋白激酶(MAPK)、表皮生长因子受体、胰岛素样生长因子、环氧合酶(COX)-2等相关信号通路防止肿瘤发生,也可通过抑制血管内皮生长因子、基质金属蛋白酶(MMP)、尿激酶纤溶酶原激活物等途径阻止肿瘤转移,有望成为一种天然的抗肿瘤药物。     

表没食子儿茶素没食子酸酯相关肿瘤临床试验研究进展

表没食子儿茶素没食子酸酯[（-）epigallo-catechingallate,EGCG]作为绿茶最主要的茶多酚,也是最主要的抗肿瘤活性成分,在肿瘤防治方面被广泛研究。在细胞和动物水平上已经证实其具有诱导肿瘤细胞凋亡、抑制侵袭转移、抑制血管生成等多种抗癌作用。现EGCG在肿瘤临床试验阶段,已经陆续出现相关的临床研究成果。本文通过整理近年来EGCG的全球肿瘤临床试验及相关成果,对其在临床试验中的安全性、防治效果以及所面临的挑战等方面的研究进展进行系统综述。      

表没食子儿茶素没食子酸酯诱导人胃癌BGC-823细胞凋亡的机制

目的:探讨表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)对人胃癌BGC-823细胞增殖的影响及其可能的机制。方法:不同浓度EGCG单独或联合c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)抑制剂SP600125作用BGC-823细胞后,应用MTT法检测BGC-823细胞的增殖抑制率,显微镜下观察细胞的形态学改变,FCM检测细胞凋亡率,蛋白质印迹法检测细胞中p-JNK和p-c-jun蛋白的表达情况,免疫细胞化学法检测细胞中caspase-3的表达。结果:EGCG可抑制BGC-823细胞的增殖(P<0.05),呈时间和剂量依赖效应;EGCG可诱导BGC-823细胞凋亡,细胞凋亡率呈剂量依赖效应(P<0.05);EGCG可上调BGC-823细胞中p-JNK、p-c-jun和caspase-3的表达(P<0.05)。EGCG引起的BGC-823细胞增殖抑制和caspase-3表达水平的上调可被SP600125部分抑制。结论:EGCG可诱导人胃癌BGC-823细胞凋亡,其作用机制可能与激活JNK信号转导途径并上调caspase-3的表达有关。     

表没食子儿茶素没食子酸酯(EGCG)抗肿瘤研究进展

表没食子儿茶素没食子酸酯（EGCG）是绿茶中主要活性成分之一，具有抑制肿瘤细胞增殖的活性。文章从EGCG在生物体内的分布及其代谢特点，诱导细胞凋亡、细胞周期阻滞以及调控癌基因、抑癌基因表达等分子机制方面综述近年来国内外对EGCG抗肿瘤研究的新进展。     

表没食子儿茶素没食子酸酯诱导人胃癌MGC-803细胞凋亡及机制

[目的]探讨表没食子儿茶素没食子酸酯(EGCG)诱导人胃癌MGC-803细胞凋亡的生物学效应及抗肿瘤机制.[方法]通过MTT还原法检测EGCG对该细胞系生长的影响;用普通光镜、流式细胞仪和DNA断裂片段分析研究EGCG诱导的细胞凋亡.S-P免疫组化法检测细胞内Bcl-2、Bax、Caspase-3蛋白的表达.[结果]EGCG能抑制MGC-803细胞的生长,抑制作用呈时间和剂量依赖性关系;EGCG处理MGC-803细胞后,普通光镜下细胞呈凋亡特征性改变;流式细胞仪示同一时间不同浓度EGCG(60、80、100、120μmol/L,48h)处理MGC-803细胞和同一浓度不同时间(80μmol/L,48、72h)处理MGC-803细胞,亚G1期细胞都逐渐增多;MGC-803细胞经EGCG(80、100、120μmol/L,48 h)后,其DNA电泳图中出现梯形条带;S-P免疫组化结果表明80μmol/L EGCG处理细胞48h后,Bcl-2蛋白表达下降,Bax和Caspase-3蛋白表达升高.[结论]EGCG有诱导人胃癌MGC-803细胞凋亡的作用,其机制可能与Bax/Bcl-2比值增高导致Caspase-3的活化从而启动细胞凋亡有关.     

表没食子儿茶素没食子酸酯诱导人胃癌BGC823细胞凋亡

[目的]观察表没食子儿茶素没食子酸酯（EGCG）诱导人胃癌BGC823细胞凋亡的生物学效应及分子机制。[方法]通过MTT法检测EGCG对BGC823细胞生长的影响;用形态学观察、流式细胞术和DNA琼脂糖凝胶电泳研究EGCG诱导BGC823细胞凋亡。West-ern blot法检测EGCG处理后BGC823细胞NF-κB（p65）、Bcl-2、Bax和Caspase-3蛋白的表达。[结果]EGCG显著性抑制BGC823细胞的生长,呈浓度依赖性。EGCG处理后,光镜下细胞呈典型的凋亡形态学改变;流式细胞术分析表明不同浓度EGCG处理48h后,亚G1期细胞逐渐增加;EGCG（80μg/ml）作用48、72h后,DNA凝胶电泳出现典型梯形条带;Western blot表明EGCG处理48h后,NF-κB（p65）和Bcl-2蛋白表达下调,Bax和Caspase-3蛋白表达升高。[结论]EGCG具有诱导人胃癌BGC823细胞凋亡的作用,其机制可能与抑制NF-κB活化,导致Bax/Bcl-2比值上调,促进Caspase-3活化有关。     

表没食子儿茶素没食子酸酯正常组织辐射防护研究进展

表没食子儿茶素没食子酸酯(EGCG)是绿茶中儿茶素的主要成分,具有保护神经、降血糖、抗氧化、抗菌、抗病毒、抗肿瘤等多种生物学功能,已被广泛应用于食品添加剂和保健品。放疗是治疗恶性肿瘤的主要手段之一,但由于其对肿瘤周围正常组织的损害,限制了放疗的治疗剂量,进而影响了肿瘤的局控率。因此,寻找一种高效无毒且具有限制肿瘤生长效...     

表没食子儿茶素没食子酸酯诱导人胃癌细胞裸鼠移植瘤凋亡的研究

背景与目的探讨绿茶提取物表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)诱导人胃癌细胞裸鼠移植瘤凋亡及分子机制。方法建立人胃腺癌(SGC7901)细胞裸鼠异种移植瘤模型,用不同剂量的EGCG进行治疗,并设对照,用流式细胞分析术检测肿瘤组织中细胞凋亡情况,免疫组织化学方法检测肿瘤组织的凋亡相关基因Bcl-2、Bax、Caspase-3的表达情况。结果裸鼠异种移植瘤治疗实验结果显示,EGCG对移植瘤生长有明显抑制作用(其中20mg/kg、EGCG抑制率54.64%与对照组比较P<0.05);PI染色FCM分析发现,EGCG20mg/kg能诱导移植瘤细胞凋亡率17.2%与对照组比P<0.05;SP免疫组织化学结果表明EGCG可上调移植瘤细胞中Bax、Caspase-3蛋白的表达,下调Bcl-2蛋白的表达。结论表没食子儿茶素没食子酸酯(EGCG)具有体内诱导人胃腺癌细胞凋亡的作用,其机制可能与Bcl-2/Bax比值降低导致Caspase-3的活化从而启动细胞凋亡有关。     

藏红花素的抗肿瘤作用

 藏红花素是从藏红花中提取出来的一种化学成分,是藏红花最主要的一种色素。近年来对宫颈癌、膀胱癌、白血病、舌鳞癌、结肠癌、胰腺癌等研究表明,藏红花素可能通过增加caspase-3 切割、调控bcl-2/bax 的比例、抑制survivin 基因的表达而诱导肿瘤细胞凋亡。通过抑制cyclin D1的表达、上调p27^kip1 蛋白表达,使细胞周期停滞,从而抑制肿瘤增殖。还可以通过脂质体包封提高细胞毒性效应,来发挥抗肿瘤作用。体内研究表明,藏红花素无明显不良反应,是一种有效的化学治疗和化学预防药物,有希望用于肿瘤临床治疗。     

双氢青蒿素的抗肿瘤作用机制

双氢青蒿素是青蒿的活性成分之一,可通过与铁离子形成自由基杀伤肿瘤细胞、诱导细胞凋亡、抗肿瘤血管生成、抑制肿瘤侵袭转移、逆转多药耐药、影响细胞内Ca2浓度、调控细胞周期、调节细胞自噬和免疫系统等方式参与抗肿瘤过程,是潜在可利用的抗肿瘤新药.     

Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis

Tea, one of the most widely consumed beverages worldwide, has been shown to have anti-cancer activity in various cancers including colon cancer. It has been demonstrated that overexpression of the inducible isoform of cyclooxygenase (COX-2) occurs during colon tumorigenesis and inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) is chemopreventive. To determine whether the anti-cancer effect associated with green tea impacted COX-2 expression levels, human colorectal cancer cell lines HT-29 and HCA-7, were treated with (-)-epigallocatechin-3-gallate (EGCG), the most abundant and effective polyphenol of green tea. EGCG significantly inhibited constitutive COX-2 mRNA and protein overexpression. The inhibitory effects of EGCG on signaling pathways controlling COX-2 expression were examined. We observed that EGCG down regulated the ERK1/2 and Akt pathways in colon cancer cells. The effect of EGCG on COX-2 expression resulted in decreased COX-2 promoter activity via inhibition of nuclear factor kappaB (NF-kappaB) activation. EGCG also promoted rapid mRNA decay mediated through the COX-2 3'untranslated region (3'UTR). In conclusion, these data suggest that inhibition of COX-2 is a mechanism for the anti-proliferative effect of green tea and emphasizes the role that dietary factors have as anti-cancer agents.     

信号传导和转录激活因子3在恶性肿瘤中的作用

在多种人类恶性肿瘤组织及细胞系中发现有信号传导和转录激活因子3(STAT3)的异常高表达,异常活化的STAT3通过调控其下游基因如Bcl-xL、Cyclin D1、VEGF等的表达,参与细胞的增殖、凋亡,调节新生血管的生成,在肿瘤发生发展中起重要的作用。目前以STAT3为靶点的肿瘤治疗研究已取得了初步的成果。     

Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma

Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.     

Biological significance of myeloperoxidase (MPO) on green tea component, (−)-epigallocatechin-3-gallate (EGCG)-induced apoptosis: its therapeutic potential for myeloid leukemia

The therapeutic approach to acute myeloid leukemia (AML) is usually chemotherapy, but severe side effects and complications induced by the anticancer drugs are sometimes fatal and are major problems in the clinical setting. Recently, more specifically targeted agents have been developed for the treatment of AML; however, most candidate agents for targeted therapy have yet to be translated into clinical application. Natural compounds appear to be safer than the current chemotherapeutic agents. Recently, it has been reported that reactive oxygen species (ROS) produced by natural compounds such as (−)-epigallocatechin-3-gallate (EGCG) induce apoptosis in myeloid leukemic cells. EGCG markedly induced apoptosis of myeloperoxidase (MPO)-positive myeloid leukemic cells. Treatment with EGCG caused a significant ROS production in MPO-positive leukemic cells. ROS are now thought of as signaling molecules in response to various extracellular stimuli. On the other hand, ROS may be the direct mediator of EGCG-induced apoptosis in myeloid leukemic cells. In particular, highly toxic ROS such as hydroxyl radical (·OH) generated via the H₂O₂/MPO halide system may directly mediate oxidative stress-induced apoptosis in myeloid leukemic cells.     

Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate

Cell signaling pathways, responsible for maintaining a balance between cell proliferation and death, have emerged as rational targets for the management of cancer. Emerging data amassed from various laboratories around the world suggests that green tea, particularly its major polyphenolic constituent (-)-epigallocatechin-3-gallate (EGCG), possesses remarkable cancer chemopreventive and therapeutic potential against various cancer sites in animal tumor bioassay systems and in some human epidemiologic studies. EGCG has been shown to modulate multiple signal transduction pathways in a fashion that controls the unwanted proliferation of cells, thereby imparting strong cancer chemopreventive as well as therapeutic effects. This review discusses the modulations of important signaling events by EGCG and their implications in cancer management.