Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases

Recent studies indicate that receptor tyrosine kinases (RTKs), which play important roles in cell proliferation, are one of the possible targets of green tea catechins (GTCs) in cancer cell growth inhibition. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, inhibits cell proliferation and induces apoptosis in various types of cancer cells, including colorectal cancer and hepatocellular carcinoma cells, by blocking the activation of the epidermal growth factor receptor (EGFR) family of RTKs. EGCG inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R) and VEGFR2, the other members of the RTK family, and this effect is also associated with the anticancer and chemopreventive properties of this agent. EGCG suppresses the activation of EGFR in part by altering membrane lipid organization and causing the subsequent inhibition of the dimerization and activation of this receptor. Preliminary trials have shown that GTCs successfully prevent the development and progression of precancerous lesions, such as colorectal adenomas, without causing severe adverse effects. The present report reviews evidence indicating that GTCs exert anticancer and chemopreventive effects by inhibiting the activation of specific RTKs, especially EGFR, IGF-1R, and VEGFR2, and concludes that targeting RTKs and their related signaling pathways by using tea catechins could be a promising strategy for the prevention of human cancers.     

Green tea extract: Chemistry,antioxidant properties and food applications – A review

Green tea is one of the most popular and extensively used dietary supplement in the United States. Diverse health claims have made for green tea as a trendy ingredient in the growing market for nutraceuticals and functional foods. Green tea extract contains several polyphenolic components with antioxidant properties, but the predominant active components are the flavanol monomers known as catechins, where epigallocatechin-3-gallate and epicatechin-3-gallate are the most effective antioxidant compounds. Additional active components of green tea extract include the other catechins such as epicatechin and epigallocatechin. Among these, epigallocatechin-3-gallate is the most bioactive and the most scrutinized one. Green tea polyphenols are also responsible for distinctive aroma, color and taste. Green tea extract can also be used in lipid-bearing foods to delay lipid oxidation and to enhance the shelf-life of various food products. This review outlines the chemistry, flavour components, antioxidant mechanism, regulatory status, food applications, and stability of green tea extract in food.     

Bitter melon (Momordica charantia): a natural healthy vegetable

Bitter melon provides health benefits against various ailments for improving the quality of life. It is nutrient dense plant-based food containing versatility of bioactive compounds such as alkaloids, polypeptide, vitamins, and minerals. Owing to presence of bioactive compounds, it has the ability to fight against various lifestyle related disorders, e.g. cancer insurgence, diabetes mellitus, abdominal pain, kidney (stone), fever, and scabies. Amongst bioactive moieties, p-insulin is similar to insulin whose subcutaneous injection significantly lower blood glucose levels in diabetic patients. It also contains steroidal saponins called charantin, act alike peptides and certain alkaloids that effectively control sugar level in blood. The therapeutic perspectives have been also highlighted as they are helpful in regulating blood cholesterol thus protecting the body from cardiovascular disorders like atherosclerosis. Whole fruit, seeds and leaves of bitter melon regulates impaired antioxidant status and suppress fat accumulation. Moreover, curative potential of its bioactive components and their utilization in value added food products are also the limelight of article.     

Propolis to Curb Lifestyle Related Disorders: An Overview

The natural products are gaining immense importance in the domain of nutrition to prevent various maladies and improve the quality of life. Among these, natural exudates are of significant worth as these biochemical compounds are released by various living entities having pharmacological properties for utilization in various drug developments. These natural exudates are the promising source for the discovery of new medications. Numerous bioactive moieties collected by honeybees from exudates and buds of particular trees and plants, considered to be utilized as defensive barrier with special reference to propolis. It generally contains numerous biochemical components, i.e., polyphenols, steroids, terpenoids, and amino acids. They also contain isoferulic acid, sinapinic acid, caffeic acid, and chrysin responsible for antibacterial perspectives. With special attention to propolis, it has been utilized in folk medicines due to several of its therapeutic activities, i.e., antioxidant, antidiabetic, anti-inflammatory, antiviral, and anticancer properties. In this context, it is extensively used in foodstuffs and beverages to improve health related disorders like inflammation, diabetes, heart disease, protects injured gums, and cancer insurgence. Moreover, it has been used to curtail stomatology, gastroenterology, skin lesions, and otorhinolaryngologic and respiration diseases.     

Molecular and cellular effects of green tea on oral cells of smokers: a pilot study

Studies in cell culture and laboratory animals have shown that green tea and its major component, epigallocatechin-3-gallate, inhibit cell growth and reduce tumor incidence. However, results of epidemiological studies have generated inconsistent, sometimes conflicting data regarding protection by green tea against human cancers. To clarify the findings of these laboratory studies in application to humans, we conducted a pilot intervention study with three heavy smokers (> 10 cigarettes/day) and three nonsmokers (never smokers) in order to evaluate the molecular and cellular effects of drinking green tea using human oral cells as an investigative tool. Green tea total extract (400-500 mg/cup, 5 cups/day) was administered in drinking water to the subjects for four weeks. Two oral cytology samples were taken weekly for measurements of tobacco carcinogen-induced DNA damage, including bulky adducts and oxidized bases, cell growth, DNA content, and apoptosis. The study showed that during the course of green tea administration smoking-induced DNA damage was decreased, cell growth was inhibited, and the percentage of cells in S phase was reduced, cells accumulated in G1 phase (cyclin D1 positive), DNA content became more diploid and less aneuploid, and p53, Caspase-3, and TUNEL, markers of apoptosis, were increased. The study, although preliminary, indicates that drinking green tea reduced the number of damaged cells in smokers by inducing cell growth arrest and apoptosis, a mechanism similar to that observed in cultured cells and animals. These results warrant a large-scale intervention trial to further verify the role of green tea in the prevention of oral cancer in smokers.     

Green tea: A promising anticancer agent for renal cell carcinoma

Renal cell carcinoma (RCC) is one of the most lethal amongst the urologic malignancies, comprising three percent of all human neoplasms, and its incidence appears to be rising. RCC is refractory to both chemotherapy and radiotherapy. Therefore, the discovery of new strategies for therapeutic intervention remains a priority. Green tea (Camellia sinensis) and tea polyphenols have been proposed to exert protective effects against several types of cancer, based on preclinical and clinical trial data; however, the anticarcinogenic activity of green tea towards RCC is unknown. In this study, a targeted metabolite analysis on a green tea leaves methanolic extract was performed by HPLC/DAD and the antiproliferative activity of the extract was assayed using human renal cancer cell lines A-498 and 769-P. The total phenolic content was very high (31.8% of methanolic extract), and the main compounds were flavan-3-ols (94.3% of the total phenolic content), and especially (−)-epigallocatechin-3-gallate (35.9% of the total phenolic content). In addition, two methylxanthines – theophylline and caffeine – were also present in the extract, caffeine being the most abundant. Green tea extract strongly inhibited the growth of both RCC cell lines in a concentration-dependent manner, with IC₅₀ values of 54 ± 10 and 129 ± 28 μg/ml for A-498 and 769-P cells, respectively. This is the first report showing that green tea is likely to be an effective anticancer agent for renal cell carcinoma.     

Effects of metal ions, catechins, and their interactions on prostate cancer

Prostate cancer is threatening human health heavily, for its causes are related to diet, genetic factors, and lifestyle. Metal ions, which are necessary to our health, are important factors inducing many diseases including prostate cancer in the condition of absence or excess. Epidemiological and laboratory studies provide convincing evidence that green tea prevents and cures prostate cancer. Practically, interactions of catechins, which are the main bioactive components in green tea or GTP, with metal ions have a new aspect to investigate their mechanism in preventing and curing prostate cancer. In the present paper, we summarize some research about the effects of catechins with metal ions related to prostate cancer and their interactions on prostate cancer.     

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.     

Mechanistic issues concerning cancer prevention by tea catechins

The cancer preventive activities of tea (Camellia sinensis, Theaceae) have been demonstrated in animal models for cancers at different organ sites and suggested by some epidemiological studies. Many mechanisms for cancer prevention have been proposed based on studies in cell lines, which demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events may result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, it is not known whether these are the molecular mechanisms of inhibition of carcinogenesis in animals and humans. This article discusses the key issues involved in extrapolating results from cell line studies to mechanistic information in vivo and in translating animal studies to human cancer prevention.     

Physiological and Nutraceutical Perspectives of Fructan

Functional and nutraceutical foods have captured the global market owing to trends and perceptions of consumers on the natural products and diet-health linkages. Health promoting potential of such foods has been attributed to the presence of essential bioactive moieties. Wheat, being staple food in many parts of the world, gained substantial attention of researchers particularly for the extraction of various functional components. Among these, fructan oligosaccharides in nature bestow quality of baked products and provide protection against various physiological disorders. Addition of fructan in various baked products enhances softness and color, especially in bread, and also imparts textural improvement. Moreover, fructans boost mineral absorption, hypocholesterolemic, and hypoglycemic perspectives, bifidogenic nature and controlling cancer insurgence. The benefits allied with fructan are mainly dose and time dependent. In this context, its industrial applications for vulnerable groups are increasing worldwide.     

Beneficial effects of tea and its polyphenols against prostate cancer

Tea, next to water, is the most widely consumed beverage in the world. Depending upon the level of fermentation, tea can be categorized into three types: green (unfermented), oolong (partially fermented), and black (highly to fully fermented). In general, green tea has been found to be superior to black and oolong tea in terms of antioxidant and health promoting benefits owing to the higher content of (-)-epigallocatechin-3-gallate. Tea polyphenols comprise about one-third of the weight of the dried leaf, and they exhibit biochemical and pharmacological activities including antioxidant activities, inhibition of cell proliferation, induction of apoptosis, cell cycle arrest and modulation of carcinogen metabolism. Several studies demonstrate that most tea polyphenols exert their effects by scavenging reactive oxygen species (ROS) since excessive production of ROS has been implicated in the development of a variety of ailments including cancer of the prostate gland (CaP). Using cell culture and animal model systems, molecular targets for these remarkable beneficial effects of green tea drinking on CaP prevention and therapy have been defined. Geographical and case-control studies are showing that green tea drinking could afford CaP chemopreventive effects in human population. In this review we attempt to summarize the experimental as well as the epidemiological basis for the possible role of tea and its polyphenols for chemoprevention and chemotherapy of CaP.     

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。     

Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus

We evaluated the antimicrobial activities of seven green tea catechins and four black tea theaflavins, generally referred to as flavonoids, as well as the aqueous extracts (infusions) of 36 commercial black, green, oolong, white, and herbal teas against Bacillus cereus (strain RM3190) incubated at 21 degrees C for 3, 15, 30, and 60 min. The results obtained demonstrate that (i) (-)-gallocatechin-3-gallate, (-)-epigallocatechin-3-gallate, (-)-catechin-3-gallate, (-)-epicatechin-3-gallate, theaflavin-3, 3'-digallate, theaflavin-3'-gallate, and theaflavin-3-gallate showed antimicrobial activities at nanomolar levels; (ii) most compounds were more active than were medicinal antibiotics, such as tetracycline or vancomycin, at comparable concentrations; (iii) the bactericidal activities of the teas could be accounted for by the levels of catechins and theaflavins as determined by high-pressure liquid chromatography; (iv) freshly prepared tea infusions were more active than day-old teas; and (v) tea catechins without gallate side chains, gallic acid and the alkaloids caffeine and theobromine also present in teas, and herbal (chamomile and peppermint) teas that contain no flavonoids are all inactive. These studies extend our knowledge about the antimicrobial effects of food ingredients.     

Green tea and prevention of esophageal and lung cancers

Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also have shown to suppress cell proliferation and induce apoptosis. Besides antioxidative property, green tea polyphenols have pro-oxidative activities under certain conditions and modulate phase II metabolic enzymes that can enhance the detoxification pathway of environmental toxicants and carcinogens. Although epidemiological studies have provided inconclusive results on the effect of green tea consumption against the development of esophageal and lung cancers in humans overall, the inverse association between green tea intake and risk of esophageal cancer risk is more consistently observed in studies with adequate control for potential confounders. Epidemiological studies also have demonstrated an inverse, albeit moderate, association between green tea consumption and lung cancer, especially in non-smokers. This article reviews data on the cancer-preventive activities of green tea extract and green tea polyphenols and possible mechanisms against the esophageal and lung carcinogenesis in experimental animals, and summarizes the current knowledge from epidemiological studies on the relationship between green tea consumption and esophageal and lung cancer risk in humans.     

Bioavailability of Tea Polyphenols

Tea is a pleasant, popular and safe beverage. Tea provides a dietary source of bioactive components to help humans reduce a wide variety of cancer risks and chronic diseases. The antioxidative activity of green tea-derived polypbenols known as catchins has been extensively studied. The reducfive effect is a synergistic action between EGCG,EGC, ECG, EC, pheophytins a and b, and other components in tealeaves, which are more bioavailable for human body.Green tea has a higher content of catechins than black tea. Green tea extract with hot water has high potential and more efficiencytoreducecancerriskthananyotherteaproductsorpureEGCG. Protein, iron, andotherfoodcomponentsmay interfere with the bioavailability of tea polyphenols. Drinkinggreentea (orpolyphenol-rich tea extract ) also enhances the cancer-preventive activity of some cancer-fighting medication such as Sulindac and Tamoxifen. Further studies are required to determine the bioavailability of green tea and cancer-preventive functionality.     

白茶的的抗突变和体外抗癌效果

本实验对两种绿茶和两种白茶进行抗突变和体外抗癌效果评价。采用Ames 实验对绿茶和白茶的抗突变特性进行比较,得出白茶的抗突变效果好于绿茶的结果。通过MTT 实验验证其抗癌效果。在400μg/ml 浓度处理下,白牡丹和白毫银针表现出对AGS 和HT-29 癌细胞的生长抑制效果好于龙井绿茶和云雾绿茶。由此得出,白茶的抗突变和体外抗癌效果好于绿茶。     

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.