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.     

Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption

Green and black tea have shown promise in the chemoprevention of prostate cancer. The objective of this study was to determine the bioavailability and bioactivity of tea polyphenols (PP) and theaflavins in human serum and human and mouse tissues. A decaffeinated black tea diet was administered to C57BL/6 mice. PPs and theaflavins were found in the small and large intestine, liver, and prostate in conjugated and free forms. The relative prostate bioavailability of theaflavin was 70% higher than that of epigallocatechin gallate (EGCG). In the second mouse study, a green tea (GT) diet was administered followed by the control diet for 1-5 d. Epicatechin (EC), EGCG, and epicatechin gallate (ECG) concentrations in prostate tissue were significantly decreased after 1 d of consuming the control diet. Epigallocatechin gallate (EGC), however, did not decrease significantly. For the human study, 20 men scheduled for surgical prostatectomy were randomly assigned to consume 1.42 L daily of GT, BT, or a caffeine-matched soda control (SC) for 5 d before radical prostatectomy. Tea PPs were greater in prostate samples from men consuming BT and GT than in men consuming SC (P = 0.0025). Although tea PP were not detectable in serum, ex vivo LNCaP prostate cancer cell proliferation was less when cells were grown in media containing patient serum collected after BT (P < 0.001) and GT (P = 0.025) consumption relative to baseline serum This is the first human study to show that tea polyphenols and theaflavins are bioavailable in the prostate where they may be active in the prevention of prostate cancer.     

Role of EGCG in Containing the Progression of Lung Tumorigenesis – A Multistage Targeting Approach

Lung cancer is a prominent form among various types of cancers, irrespective of the sex worldwide. Treatment of lung cancer involves the intensive phase of chemotherapy/radiotherapy which is associated with high rate of adverse events. There is a need of safe and reliable treatment/adjunctive therapy to apprehend the cancer by reducing the undesirable outcome of primary therapy. Epigallocatechin-3-gallate (EGCG), which is a potent antioxidant and anticancer compound extracted from the plant camellia sinensis has proved to be a novel agent to control or reduce lung tumorigenesis by affecting the signaling molecules of cell cycle regulation and apoptotic pathways. In vitro studies have revealed that EGCG can contain carcinogenesis by altering the molecules involved in multiple signal transduction pathways like ERK, VEGF, COX2, NEAT, Ras-GTPase, and kinases. The animal studies have also demonstrated effectiveness of EGCG by inhibiting various molecular pathways which include AKT, NFkB, MAPK, Bcl/Bax, DNMT1, and HIF-1α. Various attempts have been made to see the adjunctive role of EGCG in human lung cancer. Phase I/II clinical studies have recommended that EGCG is quite safe and effective in providing protection against cancer. In this review, we will discuss the role of EGCG and its molecular mechanisms in lung carcinogenesis.     

Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice

(-)-Epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinensis), has demonstrated chemopreventive activity in animal models of carcinogenesis. Previously, we reported the bioavailability of EGCG in rats (1.6%) and mice (26.5%). Here, we report that cotreatment with a second dietary component, piperine (from black pepper), enhanced the bioavailability of EGCG in mice. Intragastric coadministration of 163.8 micromol/kg EGCG and 70.2 micromol/kg piperine to male CF-1 mice increased the plasma C(max) and area under the curve (AUC) by 1.3-fold compared to mice treated with EGCG only. Piperine appeared to increase EGCG bioavailability by inhibiting glucuronidation and gastrointestinal transit. Piperine (100 micromol/L) inhibited EGCG glucuronidation in mouse small intestine (by 40%) but not in hepatic microsomes. Piperine (20 micromol/L) also inhibited production of EGCG-3"-glucuronide in human HT-29 colon adenocarcinoma cells. Small intestinal EGCG levels in CF-1 mice following treatment with EGCG alone had a C(max) = 37.50 +/- 22.50 nmol/g at 60 min that then decreased to 5.14 +/- 1.65 nmol/g at 90 min; however, cotreatment with piperine resulted in a C(max) = 31.60 +/- 15.08 nmol/g at 90 min, and levels were maintained above 20 nmol/g until 180 min. This resulted in a significant increase in the small intestine EGCG AUC (4621.80 +/- 1958.72 vs. 1686.50 +/- 757.07 (nmol/g.min)). EGCG appearance in the colon and the feces of piperine-cotreated mice was slower than in mice treated with EGCG alone. The present study demonstrates the modulation of the EGCG bioavailablity by a second dietary component and illustrates a mechanism for interactions between dietary chemicals.     

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory skin edema and ornithine decarboxylase activity by theaflavin-3,3'-digallate in mouse

Among black tea polyphenols, theaflavins were generally considered to be the most effective in cancer chemoprevention. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), and the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema and ornithine decarboxylase (ODC) activity. Topical application of these polyphenols onto the mouse resulted in inhibition of TPA-induced ear edema and skin epidermal ODC activity. The inhibitory order was as follows: TF-3 > TF-2 approximately equal to EGCG > TF-1. Western and Northern blots indicated that TF-3 significantly reduced the protein and mRNA levels of ODC in TPA-treated mouse skin and NIH 3T3 cells, whereas EGCG showed less activity. EGCG and TF-3 were able to inhibit the ODC enzyme activity in vitro. Furthermore, TF-3 also significantly reduced the basal promoter activity of the ODC gene in NIH 3T3 cells that were transiently transfected with ODC reporter plasmid. These results suggested that TF-3 was a potential inhibitor of ODC activity and TPA-induced edema and might be effective in cancer chemoprevention.     

茶多酚和表没食子儿茶素没食子酸酯对血管紧张素Ⅱ诱导的心肌肥大的抑制作用

目的体外实验观察茶多酚和表没食子儿茶素没食子酸酯(EGCG)对血管紧张素Ⅱ(AngⅡ)诱导的心肌肥大的抑制作用。方法采用乳鼠心肌细胞原代培养的方法,用AngⅡ处理心肌细胞作为心肌肥大阳性组,观察10、50和100μg/ml的茶多酚和EGCG对AngⅡ诱导的心肌肥大的抑制作用。结果与对照组相比,AngⅡ阳性组心肌细胞总蛋白含量增加、心肌细胞直径增大,而给予不同浓度的茶多酚和EGCG后,与AngⅡ阳性组相比,心肌细胞总蛋白含量和心肌细胞直径则均有一定程度的减少,并呈剂量-效应关系,但细胞数却没有变化。MTT增殖实验显示,AngⅡ可诱导心肌成纤维细胞的增殖,而给予茶多酚和EGCG后对成纤维细胞的增殖则具有一定程度的抑制作用。结论茶多酚和EGCG对AngⅡ诱导的心肌肥大有一定的抑制作用。     

Tea beverage in chemoprevention of prostate cancer: a mini-review

Because prostate cancer has a long latency period and is typically diagnosed in elderly men, it represents an ideal candidate disease for chemoprevention. Therefore, even a modest delay achieved through intervention could have a significant impact on the outcome of this disease. Epidemiological and laboratory studies have provided convincing evidence that diet, genetic factors, and lifestyle are major causes of prostate cancer. Although surgery, radiotherapy, and hormone therapy are the most widely accepted curative options for a selected group of patients suffering from prostate cancer, the side effects of these treatments are many. In recent years, many dietary agents have been being described that show a wide range of chemopreventive effects in cell culture and selected animal model systems of prostate carcinogenesis. One such agent is the beverage tea, which, next to water, is the most popularly consumed beverage in the world. The epidemiological studies and recent data, amassed from various laboratories around the world, provide evidence that tea polyphenols such as epigallocatechin-3-gallate, epigallocatechin, and epicatechin-3-gallate may have the potential to lower the risk of prostate cancer in the human population. Recently, it has been shown that green tea polyphenols, when given to TRAMP, a transgenic mouse model that mimics progressive forms of human prostate cancer, exert remarkable preventive effects against prostate cancer development. Chemoprevention of prostate cancer by tea polyphenols appears to occur through the modulation of various molecular targets. This article attempts to address the issue of the possible use of tea, especially green tea, for the chemoprevention of prostate cancer.     

EGCG和红茶多酚对HepG_2细胞脂质代谢相关基因表达的影响

目的:探讨表没食子儿茶素没食子酸酯(EGCG)和红茶多酚对人肝细胞癌HepG2细胞脂质代谢相关基因表达的影响。方法:HepG2细胞经EGCG(5μmol/L),红茶多酚(5μg/ml)或0.1%二甲亚枫(对照组)处理8h后,抽提RNA,并杂交至人14kcDNA芯片进行基因表达谱分析。应用实时RT-PCR技术对芯片结果进行验证。结果:HepG2细胞经EGCG和红茶多酚处理后表达差异的脂质代谢相关基因数分别为13条和29条,其中表达差异一致的基因有6条。实时RT-PCR结果与芯片结果一致。结论:EGCG和红茶多酚影响脂质代谢的机制是复杂的,此次实验发现的新靶标为今后茶多酚降脂作用研究提供了新的依据。     

茶多酚、茶色素对人肝癌细胞株HepG2端粒酶活性的影响

目的　利用人肝癌细胞株HepG2观察茶多酚和茶色素对端粒酶活性的影响。方法采用TRAP PCR ELISA方法对HepG2细胞端粒酶活性进行定性和定量检测。结果　TRAP PCR定性分析表明空白对照组、茶多酚组和茶色素组均端粒酶阳性 ;ELISA定量结果显示 ,5 0mg/L和 10 0mg/L茶多酚组端粒酶活性 (A450 690 值 )分别为 1 5 6和 1 4 6 ;5 0mg/L和 10 0mg/L茶色素处理组为 1 5 5和1 4 9,与空白对照组 (A450 690 值为 2 11)相比 ,茶多酚和茶色素处理后HepG2细胞端粒酶活性有统计学意义。结论　茶多酚和茶色素显著抑制HepG2细胞端粒酶活性 ,端粒酶活性可能是癌症化学预防研究的一个有用的生物标志物     

茶多酚和茶色素对肝癌细胞株HepG2细胞周期的影响

为探讨茶对肝癌细胞周期的影响 ,体外培养人肝癌细胞株HepG2 ,加入终浓度为 50mg L和 1 0 0mg L茶多酚和茶色素作用 48h后 ,流式细胞仪分析DNA含量 ,Westernblot观察对细胞周期蛋白P2 1 WAF1 CIP1 和细胞周期素D1 (cyclinD1 ) ,RT PCR检测细胞周期素依赖激酶 4 (Cdk4)在mRNA水平上的表达情况。结果表明 ,茶多酚和茶色素引起了细胞周期G1 期阻滞 (G1 arrest) ,抑制了cyclinD1蛋白的表达 ,诱导了P2 1 WAF1 CIP1 蛋白的表达增加 ,并且显著抑制了Cdk4在mRNA水平上的表达。因此 ,诱导细胞周期阻滞可能是茶预防肿瘤的一个重要机制     

茶叶防癌有效成分的筛选一茶多酚类

选用一组体外短测指标对茶水冻干物、茶多酚及表没食子儿茶素表没食子酸酯（ＥＧＣＧ），表儿茶素表没食子酸酯（ＥＣＧ），表没食子儿茶素（ＥＧＣ）和表儿茶素（ＥＣ）四种儿茶素的防癌作用进行了检测。研究结果表明，茶木冻干物、茶多酚及四种儿茶素在代表起动阶段的基因突变及微核形成两项指标中，均表现出一定的抑制作用，并有剂量－反应关系。在四种儿茶素中，ＥＣＧ对微核形成的抑制率明显高于其它三种儿茶素。在促癌阶段方面，ＥＣＧ和ＥＧＣＧ对ＴＰＡ抑制Ｖ７９细胞代谢协作具有明显的阻断作用。这两种儿茶素的抗促癌作用在ＢＡＬＢ／Ｃ３Ｔ３细胞转化试验中得到了进一步的证实。以上受试物对癌细胞的体外生长均有抑制作用，但并无特异性。本文结果表明，Ｖ７９细胞基因正向突变和细胞周期阻断法微核试验作为起始阶段指标、Ｖ７９细胞代谢协作试验作为促癌阶段、Ｈｅｌａ细胞存活率及软琼脂生长能力的测定作为癌细胞增殖指标，适用于茶中防癌有效成分的筛检。     

Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG) and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.     

绿茶及其有效成分对肾性高血压大鼠左室肥厚抑制作用的研究

目的研究绿茶及其提取物对肾性高血压大鼠左室肥厚的抑制作用机制。方法雄性Wistar大鼠160只,体重180~220g,随机分为5组,建立二肾一夹法大鼠肾性高血压左室肥厚模型:假手术组(SHAM)和手术组(2K1C)正常饮水;手术+绿茶组(2K1C+GT)饮用2%绿茶水;手术+茶多酚组(2K1C+TP)饮用0.1%茶多酚水;手术+EGCG组(2K1C+EGCG)饮用0.05%EGCG水,术后即给予不同浓度的绿茶及其提取物,持续8周直至实验结束。结果与假手术组比较,手术组和各饮茶组血压、左心室与体重比值(LVW/BW)和左心室壁厚度(LVWT)均显著升高(P<0.01)。而与手术组相比,不同浓度的绿茶及其有效成分(2%绿茶、0.1%茶多酚、0.05%EGCG)左心室重/体重(LVW/BW)、左心室壁厚度显著降低,抗氧化酶(SOD和GSH-Px)的活性升高,活性氧自由基(ROS)以及Ras和ERK1/2蛋白表达降低,但对大鼠收缩压无显著性影响。结论绿茶及其提取物对肾性高血压大鼠左室肥厚有抑制作用,其机制可能是由于茶及其有效成分具有抗氧化活性,能够清除ROS,以及对Ras-MAPK信号传导通路的调控有关。     

Review: Green Tea Polyphenols in Chemoprevention of Prostate Cancer: Preclinical and Clinical Studies

The prevention of prostate cancer (PCa) is a crucial medical challenge in developed countries. PCa remains surrounded by puzzles in spite of the considerable progress in research, diagnosis, and treatment. It is an ideal target for chemoprevention, as clinically significant PCa usually requires more than two decades for development. Green tea and its major constituent epigallocatechin gallate (EGCG) have been extensively studied as a potential treatment for a variety of diseases including cancer. In this review, we highlight the evidences of green tea polyphenols from preclinical and clinical studies in the chemoprevention/chemotherapy of PCa.     

From tea to treatment; epigallocatechin gallate and its potential involvement in minimizing the metabolic changes in cancer

As the most abundant bioactive polyphenol in green tea, epigallocatechin gallate (EGCG) is a promising natural product that should be used in the discovery and development of potential drug leads. Due to its association with chemoprevention, EGCG may find a role in the development of therapeutics for prostate cancer. Natural products have long been used as a scaffold for drug design, as their already noted bioactivity can help accelerate the development of novel treatments. Green tea and the EGCG contained within have become associated with chemoprevention, and both in vitro and in vivo studies have correlated EGCG to inhibiting cell growth and increasing the metabolic stress of cancer cells, possibly giving merit to its long utilized therapeutic use in traditional therapies. There is accumulating evidence to suggest EGCG's role as an inhibitor of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling cascade, acting upon major axis points within cancer survival pathways. The purpose of this review is to examine the research conducted on tea along with EGCG in the areas of the treatment of and/or prevention of cancer. This review discusses Camellia sinensis as well as the bioactive phytochemical compounds contained within. Clinical uses of tea are explored, and possible pathways for activity are discussed before examining the evidence for EGCG's potential for acting on these processes. EGCG is identified as being a possible lead phytochemical for future drug design investigations.     

Black tea and health

Summary   Tea is the second most consumed beverage in the world after water. Health benefits have been associated with tea drinking, including a lower risk of coronary heart disease (CHD) and cancer, and protection against dental caries and bone loss. It is likely that these benefits relate to the high polyphenol content of tea and how these polyphenols are metabolised and used by the body. In contrast, concern has arisen about the impact of tea on hydration and iron status, and the role of tea as a source of caffeine. This article updates an earlier systematic review by including more recent published evidence on the potential role of black tea in human health. While it is clear from in vitro and animal research that tea polyphenols act as antioxidants and have a beneficial effect on many biochemical processes in the body via a range of complex mechanisms, findings from epidemiological studies and the few available human intervention studies have been contradictory. Reasons for this are explored, including the influence of lifestyle factors other than tea consumption on cancer or CHD risk. The clearest consistent evidence points to an association between tea consumption, in excess of three cups per day, and a reduced risk of myocardial infarction. More human research is needed to draw conclusions about cancer and other markers of CHD. There was no consistent evidence pointing to a detrimental effect of tea drinking on hydration, bone health or iron status. The caffeine content of tea was modest compared with other sources and was unlikely to have an adverse effect on health within an intake range of 1 to 8 cups of tea per day.     

Inhibition of green tea polyphenol EGCG((−)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway

(?)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, could affect carcinogenesis and development of many cancers. However, the effects and underlying mechanisms of EGCG on gastric cancer remain unclear. We found that EGCG significantly inhibited proliferation and increased apoptosis of SGC-7901 cells in vitro. The decreased expressions of p-β-catenin(Ser552), p-GSK3β(S9) and β-catenin target genes were detected in SGC-7901 cells after treated by EGCG. XAV939 and β-catenin plasmid were further used to demonstrate the inhibition of EGCG on canonical Wnt/β-catenin signalling. Moreover, EGCG significantly inhibited gastric tumour growth in vivo by inhibiting Wnt/β-catenin signalling. Taken together, our findings establish that EGCG suppressed gastric cancer cell proliferation and demonstrate that this inhibitory effect is related to canonical Wnt/β-catenin signalling. This study raises a new insight into gastric cancer prevention and therapy, and provides evidence that green tea could be used as a nutraceutical beverage.     

茶多酚对人肝癌细胞激活蛋白1及细胞周期影响

目的 观察茶多酚对人肝癌细胞激活蛋白1（AP—1）及细胞周期的影响。方法 构建AP-1报告质粒测量AP-1活性，免疫组化测量细胞周期素D1和细胞周期素依赖激酶4表达变化，流式细胞仪分析细胞周期。结果 茶多酚抑制AP-1活性，细胞周期索Dl和细胞周期素依赖激酶4表达降低，细胞阻滞在Gl期。结论 茶多酚可能通过下调AP-1活性使细胞周期索Dl表达降低；而茶多酚使细胞周期素依赖激酶4表达降低，可能与AP-1的活性无关。