Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea
In the era of personalized medicine, selecting the ideal treatment modality for head and neck cancer is becoming more complex. Also, despite the use of the newest agents, overall survival has not been improved notably over the past few decades. Currently, in accordance with the development of diagnostic tools, prevention and early detection of cancer are being emphasized more in obtaining better treatment outcomes. Among the various cancer preventative methods, the use of green tea is one of the most common approaches, and tea is known to be involved in multiple steps of carcinogenesis. Thus, in this short review, the protective roles of green tea components against the initiation, progression, and metastasis of head and neck malignancies will be discussed. Conclusion ... green tea component, EGCG, may be the single most important agent, which has demonstrated positive effects in preventing and treating head and neck cancers. EGCC protects against diverse steps in cancer progression and invasion through multiple and complex signal transduction pathways.....
Department of Immunology, School of Medicine, Keimyung University, Daegu, Korea
Abstract Epigallocatechin-3-gallate (EGCG) is a type of catechin found in green tea. EGCG exhibits a variety of activities, including anti-inflammatory, antidiabetes, antiobesity, and antitumor. In this review, we focus on the antitumor effects of EGCG. EGCG inhibits carcinogen activity, tumorigenesis, proliferation, and angiogenesis, and induces cell death. These effects are associated with modulation of reactive oxygen species (ROS) production. Although EGCG has a dual function of antioxidant and pro-oxidant potential, EGCG-mediated modulation of ROS production is reported to be responsible for its anticancer effects. The EGCG-mediated inhibition of nuclear factor-κB signaling is also associated with inhibition of migration, angiogenesis, and cell viability. Activation of mitogen-activated protein kinases activity upregulates the anticancer effect of EGCG on migration, invasion, and apoptosis. In addition, EGCG could also induce epigenetic modification by inhibition of DNA methyltransferase activity and regulation of acetylation on histone, leading to an upregulation of apoptosis. Although EGCG promotes strong anticancer effects by multiple mechanisms, further studies are needed to define the use of EGCG in clinical treatment.
Combination of Selenium and Green Tea Improves the Efficacy of Chemoprevention in a Rat Colorectal Cancer Model by Modulating Genetic and Epigenetic Biomarkers Ying Hu mail, Graeme H. McIntosh, Richard K. Le Leu, Laura S. Nyskohus, Richard J. Woodman,Graeme P. Young
Abstract Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1ppm selenium as selenium-enriched milk protein, or combination of 1ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ß-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P<0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P<0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ß-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.
Abstract Extracts of green tea and green tea polyphenols have exhibited inhibitory effects against the formation and development of tumors at different organ sites in animals. These include animal models for skin, lung, oral cavity, esophagus, stomach, intestine, colon, liver, pancreas, bladder, mammary gland, and prostate cancers. In addition to suppressing cell proliferation, promoting apoptosis, and modulating signaling transduction, green tea polyphenols, especially (-)-epigallocatechin-3-gallate, also inhibit cell invasion, angiogenesis, and metastasis. This article reviews data on the cancer preventive activities of green tea polyphenols, possible mechanisms involved, and the relationship between green tea consumption and human cancer risk.
Conclusion The inhibitory activities of tea and tea catechins against carcinogenesis have been demonstrated in different animal models. Studies in cell lines have also showed that tea catechins can affect a variety of signaling and metabolic pathways. These molecular events could result in cancer cell growth inhibition, apoptosis, and inhibition of invasion, angiogenesis, and metastasis. These activities and the prevention of carcinogenesis have been demonstrated in animal model, but the cancer preventive activity of tea has not been consistently observed in human studies. This may be due to the relatively lower levels of tea consumption by some human populations (than animal studies) and the various confounding factors in epidemiological studies in different populations. The low bioavailability of tea polyphenols, such as EGCG, is also an issue. For agents with low systematic bioavailability, their direct contact with the digestive tract could be important for their cancer preventive activity. This point should be applicable to the activities of EGCG and polyphenols in many other foods or beverages. This information, as well as the biological properties and activities of tea polyphenols reviewed here, may be useful in design of prospective studies and in the selection of the agent, dosage, and biomarkers for intervention trials. The results of such well-designed studies will provide more definitive information on the possible use of tea for the reduction of cancer risk in different populations.
Chemoprevention of Head and Neck Cancer by Green Tea Extract: EGCG—The Role of EGFR Signaling and “Lipid Raft” Muneyuki Masuda,1 Takahiro Wakasaki,2 Satoshi Toh,2 Masahito Shimizu,3 and Seiji Adachi4
1Department of Otorhinolaryngology and Head and Neck Surgery, Kyushu Koseinenkin Hospital, 2-1-1, Kishinoura, Nishiku, Kitakyushu 806-8501, Japan 2Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan 3Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan 4Deptartment of Pharmacology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
Abstract Over the past decade dose-intensified chemo-radiotherapy or molecular targeted therapy has been introduced into the treatments of head and neck squamous cell carcinoma (HNSCC) to improve the outcomes of this dismal disease. However, these strategies have revealed only limited efficacy so far. Moreover, the frequent occurrences of second primary tumor further worsen the prognosis of patients. In this context, early detection and chemoprevention appear to be a realistic and effective method to improve the prognosis as well as quality of life in patients with HNSCC. In this short paper, we discuss the potential of green tea extract, (-)-epigallocatechin-3-galate (EGCG) in HNSCC chemoprevention, focusing on two aspects that are provided recently: (1) evidence of clinical efficacy and (2) unique biological effects on “lipid raft” that emerged as an important platform of numerous biophysical functions, for example, receptor tyrosin kinases (RTKs) signalings including epidermal growth factor receptor (EGFR), which play critical roles in HNSCC carcinogenesis.
Conclusion Considering the tantalizingly marginal improvement in the treatment outcomes of patients with HNSCC, it is urgent and critical to develop novel strategy based on early detection and chemoprevention. Among numerous putative chemopreventive agents, EGCG appears to be one of the most promising natural compounds based on accumulated data and, in particular, two novel findings provided recently: (1) clinical efficacy and (2) unique biological effects on lipid rafts that are an important platform of numerous biophysical functions including RTKs signalings. A larger-scale clinical study of EGCG is highly recommended.
Source : Journal of Oncology Volume 2011 (2011), Article ID 540148, 7 pages doi:10.1155/2011/540148 Link to Full Article
Effective Prostate Cancer Chemopreventive Intervention with Green Tea Polyphenols in the TRAMP Model Depends on the Stage of the Disease
Abstract Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP.
Experimental Design: GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF)-I/IGF binding protein-3 and IGF signaling.
Results: Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common.
Conclusions:Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.
NOTE Among all cancers, prostate cancer is an ideal candidate disease for chemoprevention because it is typically diagnosed in men ages >50 years and has a high latency period (1, 2). Therefore, even a slight delay in the progression of this disease by chemopreventive intervention could result in a substantial reduction in the incidence of the disease and, more importantly, improve the quality of life of the patients (1, 2). Evidences collected from geographic, epidemiologic, and migration studies suggest that frequent consumption of green tea is associated with lower frequencies of prostate cancer in Asian population in general compared with those in western societies (3–7). Laboratory and preclinical animal studies also indicate a protective role of green tea against prostate cancer (reviewed in refs. 8–12).
We have shown previously that oral infusion of a decaffeinated polyphenolic fraction isolated from green tea at a human achievable dose (equivalent to 6 cups of green tea a day) beginning at age 8 weeks significantly inhibits prostate cancer development, progression, and its metastasis and enhances tumor-free and overall survival in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (13–15). Initial clinical trials of green tea polyphenols (GTP) involving human prostate cancer patients have produced mixed results. Choan et al. (16) evaluated the efficacy and toxicity of green tea on hormone-refractory prostate cancer. Patients with hormone-refractory prostate cancer were prescribed green tea extract capsules at a dose level of 250 mg twice daily. Although treatment was generally well tolerated, 9 of 15 patients had progressive disease within 2 months of starting therapy and 6 patients developed progressive disease after additional 1 to 4 months of therapy. The study concluded that green tea had minimal clinical activity against hormone-refractory prostate cancer. A phase II trial explored the antineoplastic effects of green tea's (6 g/d green tea, orally in 6 divided doses) in 42 patients with hormone-refractory prostate cancer (17). Tumor response, defined as a decline (≥50%) in the baseline prostate-specific antigen value, occurred in only 2% of the cohort (95% confidence interval, 1-14%), which was not sustained beyond 2 months. The study suggested that green tea carries limited antineoplastic activity, as defined by a decline in prostate-specific antigen levels, among patients with hormone-refractory prostate cancer (17).
A recent proof-of-principle clinical trial assessed the safety and efficacy of green tea consumption in volunteers with high-grade prostatic intraepithelial neoplasia (HGPIN; ref. 18). Tumor incidence was significantly lower in green tea-treated men compared with placebo-treated men. A 2-year follow-up of patients from the same study indicated that green tea effects were long-lasting (19). This study brought into focus the importance of early intervention with green tea and highlighted the significance of green tea in a purely chemopreventive setting.
We hypothesized that green tea feeding is more effective at early stages of prostate cancer development than at the later stages. This study, therefore, was designed to assess the effectiveness of oral feeding of GTP at defined stages of prostate cancer development and progression in the autochthonous transgenic TRAMP model. Alternatively, this preclinical study was intended to assess the appropriateness of the stage of prostate cancer patients that could benefit from green tea consumption.
The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. Su-Ni Tang, Chandan Singh, Dara Nall, Daniel Meagher, Sharmila Shankar, and Rakesh K Srivastava
Background Much attention has been recently focused on the role of cancer stem cells (CSCs) in the initiation and progression of solid malignancies. Since CSCs are able to proliferate and self-renew extensively due to their ability to express anti-apoptotic and drug resistant proteins, thus sustaining tumor growth. Therefore, the strategy to eradicate CSCs might have significant clinical implications. The objectives of this study were to examine the molecular mechanisms by which epigallocathechin gallate (EGCG) inhibits stem cell characteristics of prostate CSCs, and synergizes with quercetin, a major polyphenol and flavonoid commonly detected in many fruits and vegetables.
Results Our data indicate that human prostate cancer cell lines contain a small population of CD44+CD133+ cancer stem cells and their self-renewal capacity is inhibited by EGCG. Furthermore, EGCG inhibits the self-renewal capacity of CD44+alpha2beta1+CD133+ CSCs isolated from human primary prostate tumors, as measured by spheroid formation in suspension. EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs. Furthermore, EGCG inhibits epithelial-mesenchymal transition by inhibiting the expression of vimentin, slug, snail and nuclear beta-catenin, and the activity of LEF-1/TCF responsive reporter, and also retards CSC's migration and invasion, suggesting the blockade of signaling involved in early metastasis. Interestingly, quercetin synergizes with EGCG in inhibiting the self-renewal properties of prostate CSCs, inducing apoptosis, and blocking CSC's migration and invasion. These data suggest that EGCG either alone or in combination with quercetin can eliminate cancer stem cell-characteristics.
Conclusion Since carcinogenesis is a complex process, combination of bioactive dietary agents with complementary activities will be beneficial for prostate cancer prevention and/or treatment.
Inhibitory Effects of Orally Administered Green Tea, Black Tea, and Caffeine on Skin Carcinogenesis in Mice Previously Treated with Ultraviolet B Light (High-Risk Mice) Relationship to Decreased Tissue Fat
Yao-Ping Lu, You-Rong Lou, Yong Lin,Weichung Joe Shih, Mou-Tuan Huang,Chung S. Yang, and Allan H. Conney2 Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8020 [Y-P. L., Y-R. L., M-T. H., C. S. Y., A. H. C.]; University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901 [Y. L., W. J. S.]; and The Cancer Institute of New Jersey, New Brunswick, New Jersey 08901 [Y. L., W. J. S., M-T. H., C. S. Y., A. H. C.]
Abstract Treatment of SKH-1 hairless mice with ultraviolet B light (UVB; 30 mJ/cm2) twice a week for 22 weeks resulted in tumor-free animals with a high risk of developing malignant and nonmalignant skin tumors during the next several months in the absence of additional UVB treatment (high-risk mice). Oral administration of green tea or black tea (6 mg tea solids/ml) to UVB-pretreated high-risk SKH-1 mice for 23 weeks after stopping UVB treatment decreased the number of tumors/mouse, decreased the size of the parametrial fat pads, and decreased the thickness of the dermal fat layer away from tumors and directly under tumors. Administration of the decaffeinated teas had little or no effect on these parameters, and adding caffeine (equivalent to the amount in the regular teas) to the decaffeinated teas restored their inhibitory effects. Administration of caffeine alone also decreased the number of tumors/mouse, the size of the parametrial fat pads, and the thickness of the dermal fat layer away from tumors and under tumors. Using data from individual mice and linear regression and correlation analysis, we found a highly significant positive correlation between the thickness of the dermal fat layer away from tumors and the number of tumors/mouse (r = 0.34; P = 0.0001), but the correlation between average tumor size/mouse and the thickness of the dermal fat layer away from tumors was weak (r = 0.16; P = 0.034). The results suggested that p.o. administered tea or caffeine may have decreased tumor multiplicity in part by decreasing fat levels in the dermis. Additional analysis revealed that oral administration of caffeinated beverages (green tea, black tea, decaffeinated green tea plus caffeine, decaffeinated black tea plus caffeine, or caffeine alone) decreased the thickness of the dermal fat layer under large tumors to a much greater extent than under small tumors. This is the first demonstration of a close association between inhibition of carcinogenesis and the lowering of tissue fat levels by a chemopreventive agent.
Prospective Cohort Study of Green Tea Consumption and Colorectal Cancer Risk in Women Gong Yang, Xiao-Ou Shu, Honglan Li, Wong-Ho Chow, Bu-Tian Ji, Xianglan Zhang, Yu-Tang Gao, Wei Zheng
1Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee; 2Shanghai Cancer Institute, Shanghai, China; and 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland
Abstract Teaand its constituents have shown anticarcinogenic activities in in vitroand animal studies. Epidemiologic studies, however, have been inconsistent. We prospectively evaluated the association between greentea consumption andcolorectalcancer (CRC) risk in a cohort of 69,710 Chinese women aged 40 to 70 years. Information on tea consumption was assessed through in-person interviews at baseline and reassessed 2 to 3 years later in a follow-up survey. During 6 years of follow-up, 256 incident cases of CRC were identified. The multivariate relative risk of CRC was 0.63 (95% confidence interval, 0.45-0.88) for women who reported drinking greentea regularly at baseline compared with nonregular tea drinkers. A significant dose-response relationship was found for both the amount of tea consumed (P trend = 0.01) and duration in years of lifetime tea consumption (P trend = 0.006). The reduction in risk was most evident among those who consistently reported to drink tea regularly at both the baseline and follow-up surveys (relative risk, 0.43; 95% confidence interval, 0.24-0.77). The inverse association with regular tea drinking was observed for both colon and rectal cancers. This study suggests that regular consumption of green tea may reduce CRC risk in women.
Targeting Receptor Tyrosine Kinases for Chemoprevention by Green Tea Catechin, EGCG
Masahito Shimizu *, Yohei Shirakami and Hisataka Moriwaki Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan Abstract: Tea is one of the most popular beverages consumed worldwide. Epidemiologicstudies show an inverse relationship between consumption of tea, especially green tea, and development of cancers. Numerous in vivo and in vitro studies indicate strongchemopreventive effects for green tea and its constituents against cancers of various organs. (–)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, appears tobe the most biologically active constituent in tea with respect to inhibiting cell proliferation and inducing apoptosis in cancer cells. Recent studies indicate that thereceptor tyrosine kinases (RTKs) are one of the critical targets of EGCG to inhibit cancer cell growth. EGCG inhibits the activation of EGFR (erbB1), HER2 (neu/erbB2) and alsoHER3 (neu/erbB3), which belong to subclass I of the RTK superfamily, in various types of human cancer cells. The activation of IGF-1 and VEGF receptors, the other members of RTK family, is also inhibited by EGCG. In addition, EGCG alters membrane lipidorganization and thus inhibits the dimerization and activation of EGFR. Therefore, EGCG inhibits the Ras/MAPK and PI3K/Akt signaling pathways, which are RTK-related cellsignaling pathways, as well as the activation of AP-1 and NF-κB, thereby modulating the expression of target genes which are associated with induction of apoptosis and cell cycle arrest in cancer cells. These findings are significant because abnormalities in theexpression and function of RTKs and their downstream effectors play a critical role in the development of several types of human malignancies. In this paper we review evidenceindicating that EGCG exerts anticancer effects, at least in part, through inhibition of activation of the specific RTKs and conclude that targeting RTKs and related signalingpathway by tea catechins might be a promising strategy for the prevention of human cancers.
Conclusions This review presents evidence that the inhibitory effects of EGCG on carcinogenesis are mediated, at least, through the regulation of some members of RTKs and cell signaling pathways, whereas other mechanisms also play a role in inducing an anti-cancer effect . Finally, we would like to emphasize that, in current studies, it is very significant to design and develop chemopreventive agents that act on specific molecular and cellular targets. We also therefore believe that EGCG may be a potent phytochemical because of its specific effect on targeting both RTKs and multiple pathways
Tea Polyphenols and Their Roles in Cancer Prevention and Chemotherapy
Di Chen * and Q. Ping Dou
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA
Abstract: Many plant-derived, dietary polyphenols have been studied for their chemopreventive and chemotherapeutic properties against human cancers, including green tea polyphenols, genistein (found in soy), apigenin (celery, parsley), luteolin (broccoli), quercetin (onions), kaempferol (broccoli, grapefruits), curcumin (turmeric), etc. The more we understand their involved molecular mechanisms and cellular targets, the better we could utilize these “natural gifts” for the prevention and treatment of human cancer. Furthermore, better understanding of their structure-activity relationships will guide synthesis of analog compounds with improved bio-availability, stability, potency and specificity. This review focuses on green tea polyphenols and seeks to summarize several reported biological effects of tea polyphenols in human cancer systems, highlight the molecular targets and pathways identified, and discuss the role of tea polyphenols in the prevention and treatment of human cancer. The review also briefly describes several other dietary polyphenols and their biological effects on cancer prevention and chemotherapy.
Conclusion Natural compounds have been extensively studied and have shown anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. However, further investigations are needed, especially focusing on molecular targets, mechanism-based animal and clinical studies to fully realize their potential usages and biological activities. Additionally, biological activities of these natural compounds are generally not potent enough and higher concentrations would be required to achieve the expected biological effects. Furthermore there are bioavailability and stability issues associated with some natural compounds. Therefore, based on chemical structures of natural compounds to synthesize more analogical compounds with greater potency and more stable properties is another important topic for investigation. By comparison of the structure-activity relationship (SAR) between natural and synthetic compounds, scientists have developed a series of novel analog compounds with improved bioavailability and potency of antitumor activity, compared with the natural parent compounds. These synthetic compounds include a Pro-drug of EGCG synthesized in our laboratories  and curcumin analogs such as GO-Y016, GO-Y030 and GO-Y031 . These successful examples will encourage researchers to synthesize, screen and discover more and better natural compound analogs that will eventually benefit cancer patients in the clinic
The effects of tea extracts on proinflammatory signaling
Frank Pajonk1 , Anja Riedisser2 , Michael Henke2 , William H McBride1 and Bernd Fiebich3 1 Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1714, USA 2 Department of Radiation Oncology, University Hospital of Freiburg, Germany 3 Department of Psychiatry, University Hospital of Freiburg, Germany
Abstract Background Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea.
Methods Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1β, IL-6, IL-8, TNFα and PGE2 release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-κB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays.
Results Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation
Conclusion Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate.
We conclude that tea extracts are efficient means to treat radiation-induced skin toxicity. Understanding the underlying molecular mechanisms in the future may establish tea extracts as a cheap and broadly available treatment for skin toxicity caused by ionizing radiation in industrial as well as developing countries during clinical radiotherapy and in case of accidents involving ionizing radiation.
University of Wisconsin School of Pharmacy, Division of Pharmacy Practice, 1031 Rennebohm Hall, Madison, WI, USA. firstname.lastname@example.org
Abstract Every year nearly 200,000 men in the United States are diagnosed with prostate cancer (PCa), and another 29,000 men succumb to the disease. Within certain regions of the world population based studies have identified a possible role for green tea in the prevention of certain cancers, especially PCa. One constituent in particular, epigallocatechin-3-gallate also known as EGCG has been shown in cell culture models to decrease cell viability and promote apoptosis in multiple cancer cell lines including PCa with no effect on non-cancerous cell lines. In addition, animal models have consistently shown that standardized green tea polyphenols when administered in drinking water delay the development and progression of PCa. Altogether, three clinical trials have been performed in PCa patients and suggest that green tea may have a distinct role as a chemopreventive agent. This review will present the available data for standardized green tea polyphenols in regard to PCa chemoprevention that will include epidemiological, mechanism based studies, safety, pharmacokinetics, and applicable clinical trials. The data that has been collected so far suggests that green tea may be a promising agent for PCa chemoprevention and further clinical trials of participants at risk of PCa or early stage PCa are warranted.
Conclusion What has become evident over time is the necessity to use standardized green tea polyphenols for interventional purposes as opposed to a green tea infusion. This is an important point to illustrate being that with a green tea infusion there is no assurance of the contents of the infusion being that environment, cultivation, and brewing technique can influence the content of a green tea infusion. This point could not be further illustrated in the example of a previous clinical trial that evaluated an unstandardized green tea infusion in metastatic prostate cancer patients. Regrettably, the results of this study halted a second study where several patients receiving what is now considered a low dose of green tea extract showed a delay in the elevation of PSA in several patients. As mentioned earlier a recent clinical trial has now been performed using a standardized green tea extract (e.g. Polyphenon E) in patients undergoing radical prostatectomy a decrease in prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients is observed (McLarty et al. 2009). It is imperative that future studies that are evaluating plant based materials be well characterized before clinical trials are performed. The evidence that has been collected by multiple investigators suggests that green tea may be a promising agent for PCa chemoprevention and further clinical trials of participants at risk of PCa or early stage PCa are warranted.
LINK TO FULL ARTICLE Green tea (Camellia sinensis) and cancer prevention: a systematic review of randomized trials and epidemiological studies
Jianping Liu1,2,3 , Jianmin Xing1 and Yutong Fei1
1 Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China 2 National Research Centre in Complementary and Alternative Medicine (NAFKAM), University of Tromso, Norway 3 Division of Chinese Medicine, RMIT University, Melbourne, Australia
Background Green tea is one of the most popular beverages worldwide. This review summarizes the beneficial effects of green tea on cancer prevention.
Methods Electronic databases, including PubMed (1966–2008), the Cochrane Library (Issue 1, 2008) and Chinese Biomedical Database (1978–2008) with supplement of relevant websites, were searched. There was no language restriction. The searches ended at March 2008. We included randomized and non-randomized clinical trials, epidemiological studies (cohort and case-control) and a meta-analysis. We excluded case series, case reports, in vitro and animal studies. Outcomes were measured with estimation of relative risk, hazard or odd ratios, with 95% confidence interval.
Results Forty-three epidemiological studies, four randomized trials and one meta-analysis were identified. The overall quality of these studies was evaluated as good or moderate. While some evidence suggests that green tea has beneficial effects on gastrointestinal cancers, the findings are not consistent.
Conclusion Green tea may have beneficial effects on cancer prevention. Further studies such as large and long term cohort studies and clinical trials are warranted
Epicatechins Purified from Green Tea (Camellia sinensis) Differentially Suppress Growth of Gender-Dependent Human Cancer Cell Lines
Mepur H. Ravindranath1, Thiruverkadu S. Saravanan1, Clarence C. Monteclaro1, Naftali Presser1, Xing Ye1, Senthamil R. Selvan2 and Stanley Brosman3 1
Department of Glycoimmunotherapy, John Wayne Cancer Institute Santa Monica, CA, 2 Cell Biology Laboratory, Hoag Cancer Center, Hoag Memorial Hospital Presbyterian Newport Beach, CA, and 3 Pacific Clinical Research Santa Monica, CA
The anticancer potential of catechins derived from green teais not well understood, in part because catechin-related growthsuppression and/or apoptosis appears to vary with the type andstage of malignancy as well as with the type of catechin. Thisin vitro study examined the biological effects of epicatechin(EC), epigallocatechin (EGC), EC 3-gallate (ECG) and EGC 3-gallate(EGCG) in cell lines from human gender-specific cancers. Celllines developed from organ-confined (HH870) and metastatic (DU145)prostate cancer, and from moderately (HH450) and poorly differentiated(HH639) epithelial ovarian cancer were grown with or withoutEC, EGC, ECG or EGCG. When untreated cells reached confluency,viability and doubling time were measured for treated and untreatedcells. Whereas EC treatment reduced proliferation of HH639 cellsby 50%, EGCG suppressed proliferation of all cell lines by 50%.ECG was even more potent: it inhibited DU145, HH870, HH450 andHH639 cells at concentrations of 24, 27, 29 and 30 µM,whereas EGCG inhibited DU145, HH870, HH450 and HH639 cells atconcentrations 89, 45, 62 and 42 µM. When compared withEGCG, ECG more effectively suppresses the growth of prostatecancer and epithelial ovarian cancer cell lines derived fromtumors of patients with different stages of disease.
Green tea consumption and the risk of liver cancer in Japan: the Ohsaki Cohort study Journal
Cancer Causes and Control PublisherSpringer Netherlands ISSN0957-5243 (Print) 1573-7225 (Online) CategoryOriginal paper DOI10.1007/s10552-009-9388-x Subject CollectionMedicine SpringerLink DateFriday, September 18, 2009
Objectives To investigate the association between green tea consumption and liver cancer incidence. Methods We prospectively followed 41,761 Japanese adults aged 40–79 years, without a history of cancer at the baseline or any missing data for green tea consumption frequency. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, alcohol drinking, smoking, the consumption of coffee, vegetables, dairy products, fruit, fish, and soybean.
Results Over 9 years of follow-up, among 325,947 accrued person-years, the total incidence of liver cancer was 247 cases. We found that green tea consumption was inversely associated with the incidence of liver cancer. In men, the multivariate-adjusted HRs (95% CIs) for liver cancer incidence with different green tea consumption categories were 1.00 (reference) for <1 cup/day, 0.83 (0.53–1.30) for 1–2 cups/day, 1.11 (0.73–1.68) for 3–4 cups/day, and 0.63 (0.41–0.98) for ≥5 cups/day (p for trend = 0.11). The corresponding data among women were 1.00 (reference), 0.68 (0.35–1.31), 0.79 (0.44–1.44), 0.50 (0.27–0.90) (p for trend = 0.04).
Conclusions Green tea consumption is associated with a reduced risk of liver cancer incidence.
Differential Growth Suppression of Human Melanoma Cells by Tea (Camellia sinensis) Epicatechins (ECG, EGC and EGCG)
Mepur H. Ravindranath, Vaishali Ramasamy, Songeun Moon, Carlos Ruiz and Sakunthala Muthugounder
Department of Glycoimmunotherapy, John Wayne Cancer Institute, Santa Monica, CA 90404, USA We previously reported that catechins of green tea have different antiproliferative effects on celllines derived from gender-dependent cancers; epicatechin 3-gallate (ECG) had the strongest inhibitory effect. In the present study, we examined the effects of epigallocatechin (EGC),epicatechin-gallate (ECG) and EGC 3-gallate (EGCG) on the viability, density, doubling time and cycle number of cell lines derived from melanoma metastasized to lymph nodes (MB-1133and SE-0154) or distant organs (CH-0356, JK-0346, SA-1171, GE-0208, NS-1176 and LF-0023). These catechins have been documented to have no growth suppressive or apoptotic effects on normal melanocytes (Nihal et al., Int J Cancer 2005;114:513–21). EGCG (50 mM)showed greater inhibitory potency than EGC (50 mM) in SE-0154, NS-1176, GE-0208 and LF-0023 cell lines but the two catechins produced similar inhibitory effects in CH-0356,JK-0346 and SA-1171 cell lines. The IC50 (50% inhibitory concentration) was lower for EGC than EGCG in MB-1133 and CH-0356 cells, higher for EGC than EGCG in GE-0208 cells andcomparable (11–12 mM) for both the catechins in LF-0023 cells. When compared with EGC, the cytotoxic effect (% dead cell counts) and the suppression of the growth (change in cell number) of all melanoma cell lines tested were pronounced with EGCG. This investigation validates thehypothesis that anticancer action of the various catechins may vary with the type of malignancy and provides a model for tumor cell heterogeneity based on susceptibility and resistance oftumor cells to different green tea catechins. Therefore, this information is critical for undertaking chemopreventive or chemotherapeutic trials against melanoma and gender-basedcancers
Green Tea Inhibits Vascular Endothelial Growth Factor (VEGF) Induction in Human Breast Cancer Cells
Maryam R. Sartippour, Zhi-Ming Shao, David Heber,* Perrin Beatty, Liping Zhang, Canhui Liu, Lee Ellis,† Wen Liu,† Vay Liang Go* and Mai N. Brooks3 Department of Surgery, Division of Oncology and *Center for Human Nutrition, University of California, Los Angeles, CA and †University of Texas, MD Anderson Cancer Center, Houston, TX1,2
Investigators have shown that green tea and its main catechin epigallocatechin-3 gallate (EGCG) may decrease the risk of cancer. Our previous study showed that green tea extract (GTE) as well as its individual catechin components inhibited MDA-MB231 breast cancer cell and human umbilical vein endothelial cell (HUVEC) proliferation. Further, GTE suppressed breast cancer xenograft size and decreased the tumor vessel density in vivo. In the current study, we investigated the effect of GTE on the major angiogenic factor vascular endothelial growth factor (VEGF) in an in vitro experiment. GTE or EGCG (40 mg/L) significantly decreased the levels of the VEGF peptide secreted into conditioned media. This occurred in both HUVEC and human breast cancer cells and the effect was dose dependent. Furthermore, GTE and EGCG decreased the RNA levels of VEGF in MDA-MB231 cells. This inhibition occurred at the transcriptional regulation level and was accompanied by a significant decrease in VEGF promoter activity. We also showed that GTE decreased c-fos and c-jun RNA transcripts, suggesting that activator protein (AP)-1–responsive regions present in the human VEGF promoter may be involved in the inhibitory effect of GTE. Furthermore, GTE suppressed the expression of protein kinase C, another VEGF transcription modulator, in breast cancer cells. Inhibition of VEGF transcription appeared to be one of the molecular mechanism(s) involved in the antiangiogenic effects of green tea, which may contribute to its potential use for breast cancer treatment and/or prevention. J. Nutr. 132: 2307–2311, 2002.