The modulation of endothelial cell gene expression by green tea polyphenol-EGCG

Human and animal studies have shown that green tea consumption is associated with a reduced risk of some cancers. This has been attributed to its polyphenol components, in particular (-)-epigallocatechin gallate (EGCG). In addition to be a cancer chemopreventive agent, EGCG inhibits angiogenesis, thus reducing tumor growth and metastasis. We tested EGCG modulation on the gene expression profile of endothelial cells stimulated by VEGF using Affymetrix microarrays. A total of 421 genes were up-regulated and 72 genes were down-regulated at the false discovery rate of 5% by VEGF, EGCG, and EGCG pretreatment followed by VEGF stimulation. The changes in the expression of several pivotal genes were validated by real-time PCR. Furthermore, we have identified two signaling pathways (Wnt and Id) involved in cell proliferation were inhibited by EGCG treatment, suggesting the negative regulation of EGCG on cell proliferation. Our results also indicate that the antiangiogenesis effect of EGCG is partially mediated through its broad inhibition on endothelial cell proliferation. Our data further support earlier observations that the anticancer effect of EGCG is mediated through changes in the expression of genes that are associated with cell proliferation.     

Antiproliferative activity of tea catechins associated with casein micelles,using HT29 colon cancer cells

Numerous studies have shown that green tea polyphenols display anticancer activities in many organ sites by using different experimental models in rodents and in cultured cell lines in vitro. The present study tested the ability of casein micelles to deliver biologically active concentrations of polyphenols to HT-29 colon cancer cells. Epigallocatechin gallate (EGCG), the major catechin found in green tea, was used as the model molecule, as it has been shown to have antiproliferative activity on colon cancer cells. In the present work, we hypothesized that due to the binding of caseins with EGCG, casein micelles may be an ideal platform for the delivery of this bioactive molecule and that the binding would not affect the bioaccessibility of EGCG. The cytotoxicity and proliferation behavior of HT-29 colon cancer cells when exposed to free EGCG was compared with that of nanoencapsulated EGCG in casein micelles of skim milk. Epigallocatechin gallate-casein complexes were able to decrease the proliferation of HT-29 cancer cells, demonstrating that bioavailability may not be reduced by the nanoencapsulation. As casein micelles may act as protective carriers for EGCG in foods, it was concluded that nanoencapsulation of tea catechins in casein micelles may not diminish their antiproliferative activity on colon cancer cells compared with free tea catechins.     

茶叶儿茶素的癌症化学预防增效机制研究进展

研究证实,茶叶中儿茶素对预防癌症起到重要的作用,其中表没食子儿茶素没食子酸酯(EGCG)具有比较强的抗氧化、抑制癌细胞增殖和诱导细胞的凋亡能力,是化学预防癌症最具潜力的天然产物之一.作者归纳了儿茶素的生物活性、EGCG与天然抗癌产物和临床药物的增效机制研究进展,为更加深入地开展EGCG癌症化学预防机制研究提供参考.     

Effect of process unit operations and long-term storage on catechin contents in EGCG-enriched tea drink

Due to the increasing market for functional foods and the chemopreventive action of (?)-epigallocatechin gallate (EGCG), manufacturers produce ready-to-drink green tea infusions enriched or not in EGCG. However, the maintenance of green tea catechins stability in drinks is always a challenge. In this context, the objectives of this study were (1) to assess the catechin stability in tea drink during a 6-month storage, (2) to evaluate the impact of process unit operations on catechin stability and (3) to compare the catechin and caffeine contents of commercially available tea drinks. It appeared that the stability of catechins during long-term storage was optimum at low temperature (4 °C) and acidic pH (pH 4.0). During the processing of the EGCG-enriched green tea drink, all the process unit operations, except heat-treatment, had no impact on catechin concentrations. In addition, in commercially available tea drinks, except enriched green tea drinks, their catechin contents are very low to provide health benefits.     

Chemopreventive potential of the tannase-mediated biotransformation of green tea

Green tea (Camellia sinensis) is one of the most widely consumed beverages in the world. The cancer chemopreventive qualities of green tea have been well documented. Epigallocatechin gallate (EGCG) is often described as the most potently chemopreventive green tea catechin; however, the low bioavailability of EGCG is a limiting factor for its biological effect. Thus, the aim of this work was to test the chemopreventive potential of green tea extract and EGCG after tannase-mediated hydrolysis. The results showed that the biotransformed compounds retained most of the beneficial properties of the original compounds, and some beneficial properties were improved in the biotransformed compounds. Biotransformation of EGCG decreased its toxicity without affecting its antiproliferative effects. Furthermore, human cells gene expression profiling showed that the biotransformed compounds modulated the expression of several genes related to carcinogenesis. These results demonstrate the benefits of the biotechnological modification of natural food molecules, allowing the improvement of the nutraceutical potential of a beverage as green tea.     

Delphinidin inhibits a broad spectrum of receptor tyrosine kinases of the ErbB and VEGFR family

Delphinidin has been reported to inhibit EGFR signalling. To determine whether other receptor tyrosine kinases (RTKs) are also influenced by delphinidin, we examined its ability to inhibit the kinase activity of EGFR, ErbB2, VEGFR‐2, VEGFR‐3 and IGF1R in a cell‐free test system. We found that delphinidin strongly inhibited the protein tyrosine kinase activity of all tested RTKs at low micromolar concentrations. In A431 and PAE cells, ligand‐induced phosphorylation of the receptors was also potently suppressed, with a preference for the suppression of the activity of ErbB3 (IC₅₀ ? 100 nM) and VEGFR‐3 (IC₅₀ < 50 μM). Thus the inhibition of RTKs by delphinidin is not limited to cell‐free assays but is also of relevance in the cellular context. The results indicate that delphinidin acts as a broad‐spectrum inhibitor of RTKs. Given the crucial role of the receptors in tumour growth and metastasis, we conclude that delphinidin has the potential to act directly against tumour cells as well as to interfere with key tumour–host interactions, although the suitability of delphinidin as a drug in cancer management may be compromised by its limited stability. Nevertheless, delphinidin may represent a novel lead compound for the development of chemopreventative and chemotherapeutic intervention strategies.     

Anti-obesity effects of green tea: from bedside to bench

During the last decade, the traditional notion that green tea consumption benefits health has received significant scientific attention and, particularly, the areas of cardiovascular disease and cancer were subject to numerous studies. Due to the ever-growing obesity pandemic, the anti-obesity effects of green tea are being increasingly investigated in cell, animal, and human studies. Green tea, green tea catechins, and epigallocatechin gallate (EGCG) have been demonstrated in cell culture and animal models of obesity to reduce adipocyte differentiation and proliferation, lipogenesis, fat mass, body weight, fat absorption, plasma levels of triglycerides, free fatty acids, cholesterol, glucose, insulin and leptin, as well as to increase beta-oxidation and thermogenesis. Adipose tissue, liver, intestine, and skeletal muscle are target organs of green tea, mediating its anti-obesity effects. Studies conducted with human subjects report reduced body weight and body fat, as well as increased fat oxidation and thermogenesis and thereby confirm findings in cell culture systems and animal models of obesity. There is still a need for well-designed and controlled clinical studies to validate the existing and encouraging human studies. Since EGCG is regarded as the most active component of green tea, its specific effects on obesity should also be investigated in human trials.     

Comparison of catechins and aromas among different green teas using HPLC/SPME-GC

Green tea polyphenols (GTP) from Camellia sinensis (L.) O. Kuntze are the major water soluble components in tea liquor. The GTP extraction yield was determined using different extraction times from 10 to 60 min at 70°C, and also at different temperatures from 50°C to 100°C, keeping the extraction time constant. The composition of the GTP (catechins) from samples of different origins was determined by RP–HPLC, measuring the absorbance at 280 nm. The calibration curves of the catechins were linear between 5 ng and 2 μg, and their C.V. values for the quantitation were less than 4.0% for four replicates using four different sets of each type. The total epicatechin derivatives (EPD) and epigallocatechin-3-gallate (EGCG) from Azorean green tea, accounted for 74.5 and 47.9% (w/w) of the total GTP, respectively, and were compared with that from tea samples of different origins. The EGCG:caffeine ratio in Azorean green tea was fourfold higher as compared with others, which suggested a good source of a chemopreventive agent. The aroma composition of different green tea samples was compared using the SPME/GC headspace methodology.     

Absorption,metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review

Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.     

表没食子儿茶素没食子酸酯(EGCG)对癌症细胞信号传导链的影响

表没食子儿茶素没食子酸酯(EGCG)是茶叶提取活性物中的重要成分之一,也是最具潜力的天然化学预防剂之一。EGCG对多种癌细胞的多条信号通路都有影响,其对癌细胞信号传导通路影响的结果是抑制癌细胞的增殖、加速癌细胞凋亡以及抑制癌细胞转移、侵袭等。当前研究得较多的是MAPK、PI3K-Akt、NF-κB和p53信号通路。本文就近年来EGCG对不同癌症细胞信号传导链影响的研究进行综述。     

表没食子儿茶素没食子酸酯分子修饰及抗癌研究进展

表没食子儿茶素没食子酸酯((–)-epigallocatechin-3-gallate,EGCG)是茶叶中的一类重要儿茶素,在体内外实验中被证实具有广泛的抗癌活性。研究发现,其抗癌机理包含诱导细胞凋亡、抗血管生成、调控细胞周期、阻滞细胞转移、协同抗癌等,但由于多羟基的化学结构使其在中性或碱性介质中极不稳定,最终导致其生物活性利用率降低,限制了临床应用范围。已有研究表明,分子修饰能显著改善EGCG分子活性,增强其稳定性,并使其表现出较强的抗癌活性。本文首先概述EGCG分子修饰的方法,然后对EGCG及其衍生物的抗癌实例和作用机理进行归纳总结。     

In vitro human skin permeation and cutaneous metabolism of catechins from green tea extract and green tea extract-loaded chitosan microparticles

Catechins are major antioxidants in green tea (Camellia sinensis or Camellia assamica), but because they do not permeate the skin well, the application of green tea in cosmetic products has so far been limited. This study aims to evaluate the cutaneous absorption of catechins from an extract of green tea and from a green tea extract-loaded chitosan microparticle. The catechin skin metabolism was also examined. The results suggest that chitosan microparticles significantly improve the ability of catechins to permeate skin. The cutaneous metabolism of the catechins significantly affected their permeation profiles. Epicatechin (EC) and epigallocatechin (EGC) penetrated the skin more than epigallocatechin gallate (EGCG) and epicatechin gallate (ECG). The galloyl groups in EGCG and ECG were enzymatically hydrolysed to EGC and EC, respectively. Dehydroxylation of catechins was also observed. Chitosan microparticles effectively prevented enzymatic changes of the catechins; therefore, chitosan microparticles are here found to be the promising carriers for enhancing the skin permeation.     

Tea polyphenol (-)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells

Scope: The aim of this research was to explore whether the tea‐polyphenol (–)‐epigallocatechin‐3‐gallate (EGCG) could be used as a potential agent for blocking smoking (nicotine, Nic)‐ or hormone (estradiol, E2)‐induced breast cancer cell proliferation through inhibition of a common signaling pathway. Methods and results: To explore whether Nic (>0.1 μM, 24 h) and E2 (>1 nM, 24 h) significantly increased α9‐nicotinic acetylcholine (α9‐nicotinic acetylcholine receptor (nAChR)) mRNA and protein expression levels, real‐time PCR and immunoblotting analysis experiments were performed in human breast cancer (MCF‐7) cells. Luciferase promoter activity experiment was performed to test the α9‐nAChR promoter activity affected by Nic, E2 or EGCG. The results indicate that treatment with EGCG (1 μM) profoundly decreases Nic‐ and E2‐induced MCF‐7 proliferation by down regulating α9‐nAChR expression. The α9‐nAChR promoter activity is significantly induced by 24‐h treatment with Nic (10 μM) or E2 (10 nM) (>1.8 and ～2.3‐fold, respectively) in MCF‐7 cells. Pretreatment with EGCG eliminated the Nic‐ and E2‐induced α9‐nAChR promoter‐dependent luciferase activity. We further demonstrate that combined treatment with EGCG profoundly inhibits [3H]‐Nic/ α9‐nAChR binding activity in breast cancer cells. Conclusions: We found that the EGCG could be used as an agent for blocking smoking (Nic)‐ or hormone (E2)‐induced breast cancer cell proliferation by inhibiting of α9‐nAChR signaling pathway. This study reveals the novel antitumor mechanisms of EGCG, and these results may have significant applications for chemopreventive purposes in human breast cancer.     

Digestive stability and absorption of green tea polyphenols: Influence of acid and xylitol addition

The objective of this study was to determine the effect of sugar substitute and acid on digestive stability and intestinal uptake of catechins in Ready-To-Drink (RTD) green tea. Green tea extracts formulated with prescribed amounts of sucrose (200, 500, and 1000 mg), glucose (280, 700, and 1400 mg), and xylitol (200, 500, and 1000 mg) in combination with citric acid (10 mg) or vitamin C (10 mg) were subjected to an in vitro digestion model coupled with Caco-2 cells. Green tea extracts only showed a poor digestive recovery (5.3%) of total catechins and EGC and EGCG significantly decreased with the digestive recovery of 4.6% and 6.1%, respectively. However, measured amount of EGC, EGCG, or ECG in digestive fluids and caco-2 human intestinal cell significantly increased by adding citric acid or vitamin C. There was remarkable increase of digestive recovery of total catechins in green tea with xylitol/citric acid and xylitol/vitamin C by 1.7–2.5 times and 3 times, respectively, with different amounts of xylitol. It was also determined that intestinal uptake of total catechins significantly increased 6 and 11 times in green tea with xylitol/citric acid and xylitol/vitamin C, respectively, compared to green tea only.     

Chemoprevention of lung cancer by tea

Tea is the second only to water as the most consumed beverage in the world. Both green and black teas have been studied for their health benefits for a variety of diseases, particularly cancer. Lung cancer is the predominant cause of cancer mortality in developed countries. Smokers' risk of lung cancer is 20 times that of persons who have never smoked. Epidemiological studies on the cancer-preventive effects of tea produce inconsistent results, which could in part be attributed to the lack of a universal standard for tea preparations. However, most animal studies indicate that tea has strong chemopreventive effects against lung tumorigenesis. The reported mechanisms for chemopreventive activity of green tea are antioxidation, induction of phase II enzymes, inhibition of TNFalpha expression and release, inhibition of cell proliferation, and induction of apoptosis. Cell cycle arrest and apoptosis induced by green tea are probably the two most significant factors. Future studies are needed to determine how green tea affects the genes associated with cell cycle regulation and apoptosis during the mouse lung carcinogenesis process.     

Effect of various calcium concentrations on the interactions between β-lactoglobulin and epigallocatechin-3-gallate

β-Lactoglobulin (β-lg) is a globular protein accounting for 11% of all milk proteins. Recently, the use of β-lg as vehicles for the delivery of bioactive compounds such as green tea catechins has been explored. The objective of this study was to determine the impact of various calcium concentrations on the interactions between β-lg and epigallocatechin-3-gallate (EGCG), the most abundant green tea catechins. Five different calcium concentrations were tested for their effect on complex formation and characteristics. Our results showed that when EGCG was present, the increase in calcium concentration influenced ζ-potential and more importantly, drastically increased particle size. The presence of EGCG was essential to the formation of larger complexes, stabilized mainly by electrostatic interactions via calcium bridging when calcium is present.