Brain Behav Immun. 2009 Aug;23(6):721-31. Epub 2009 Mar 1.

Bioactive components of tea: cancer, inflammation and behavior.

de Mejia EGRamirez-Mares MVPuangpraphant S.


Department of Food Science and Human Nutrition, University of Illinois-Urbana-Champaign, 1201 W. Gregory Drive,Urbana, IL 61801, USA

Bioactive components of tea: Cancer, inflammation and behavior

Tea is one of the most widely consumed beverages worldwide. Several studies have suggested that catechins and theaflavins found in tea may reduce the risk of various types of cancers. Major advances have been made to understand the molecular events leading to cancer prevention; however, the evidence is not conclusive. Evidence from pre-clinical and clinical studies also suggests that persistent inflammation can progress tocancer. Several possible mechanisms of action may explain the cancer preventive aspects of tea components specifically anti-inflammatory effects. In regards to brain health, green tea catechins have been recognized as multifunctional compounds for neuroprotection with beneficial effects on vascular function and mental performance. Theanine, a unique amino acid intea, enhances cognition in humans and has neuroprotective effects. Human interventional studies with well characterized tea products are needed.




Anticancer Therapeutics and Oncology Society



Volume 2, Issue 6, Pages 350-359 (November 2002)


Muneyuki Masuda, Masumi Suzui, Jin T. E. Lim, Atsuko Deguchi, Jae-Won Soh, I. Bernard Weinstein


Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction.




Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY.




In a recent study on head and neck squamous cell carcinoma (HNSCC) cells we found that epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, inhibited activation of the epidermal growth factor receptor (EGFR) and related signaling pathways. Since activation of EGFR signaling pathways is associated with angiogenesis, we examined the effects of EGCG on vascular endothelial growth factor (VEGF) production by YCU-H891 HNSCC and MDA-MB-231 breast carcinoma cell lines, because we found that both of these cell lines display autocrine activation of transforming growth factor-? (TGF-?)/EGFR signaling and produce high levels of VEGF. Treatment with EGCG inhibited the constitutive activation of the EGFR, Stat3, and Akt in both cell lines. These changes were associated with inhibition of VEGF promoter activity and cellular production of VEGF. Mechanistic studies indicated that inhibition of Stat3, but not mitogen-activated protein kinase kinase (MEK)1 or phosphatidylinositol 3'-kinase (PI3K), significantly decreased VEGF promoter activity. However, the inhibitory effects of a dominant negative Stat3 on VEGF expression was not as strong as that produced by EGCG. An analysis of alternative pathways indicated that EGCG strongly inhibited the constitutive activation of NF-?B in both cell lines, and an NF-?B inhibitor strongly inhibited VEGF production. These results suggest that EGCG inhibits VEGF production by inhibiting both the constitutive activation of Stat3 and NF-?B, but not extracellular-signal-regulated kinase (ERK) or Akt, in these cells. Therefore, EGCG may be useful in treating HNSCC and breast carcinoma because it can exert both antiproliferative and antiangiogenic activities.




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Helping doctors help patients






Volume 165, Number 22, Pages 2683-2686 (December 2005)


Susanna C. Larsson, Alicja Wolk


Drinking Tea Associated with Lower Risk of Ovarian Cancer


Division of Nutritional Epidemiology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.


Women who drank at least two cups of tea a day had a lower risk of ovarian cancer than those who did not drink tea, according to a study in the December 12/26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Evidence from laboratory studies indicates that green and black tea preparations may protect against various cancers. But few epidemiological studies have examined the relationship specifically between tea consumption and the risk of ovarian cancer, according to background information in the article.

Susanna C. Larsson, MSc, and Alicja Wolk, DMSc, of the National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, prospectively examined the association between tea consumption and the risk of ovarian cancer in 61,057 women, aged 40 to 76, who were participants in the population-based Swedish Mammography Cohort.

Participants completed a validated 67-item food frequency questionnaire at enrollment between 1987 and 1990, and were followed for cancer incidence through December 2004. At baseline, 68% of the participants reported drinking tea (mainly black tea) at least once per month. During an average follow-up of 15.1 years, 301 women were diagnosed as having invasive epithelial ovarian cancer.

"We observed a 46% lower risk of ovarian cancer in women who drank two or more cups of tea per day compared with non-drinkers," the authors report. "Each additional cup of tea per day was associated with an 18% lower risk of ovarian cancer."

Women who drank less than one cup of tea per day had an 18% lower risk of ovarian cancer than non-drinkers. The risk was 24% lower for women who drank one cup of tea per day.

"This association does not depend on lower coffee consumption among women with high tea consumption; coffee is not associated with ovarian cancer risk in this cohort," the authors write.

"In summary, our results from a large population-based cohort of Swedish women suggest that tea consumption may lower the risk of ovarian cancer," the authors conclude. "Because prospective data on this relationship are scarce, our findings need confirmation by future studies."


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International Society of Surgery (ISS)


Volume 26, Number 6, Pages 683-686 (June 2002)


Takada M, Ku Y, Habara K, Ajiki T, Suzuki Y, Kuroda Y.

Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human biliary tract carcinoma cells.

First Department of Surgery, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku,


Based on recent evidence that tea consumption contributes to a decreased incidence of human carcinomas, a number of investigators have focused on the mechanisms of cancer prevention by tea extracts, especially green tea polyphenols. Epigallocatechin-3-gallate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. This suggests that EGCG may exert its growth-inhibitory effects through modulation of G1 regulatory proteins such as cdk2 and cdk4. The human biliary tract carcinoma cells (TGBC-2, SK-ChA-1, and NOZC-1) were treated with different doses of EGCG (0, 25, 50, 100, and 200 mM) for 48 hours in cell medium. Cell proliferation was analyzed by WST-1 colorimetric assay. For the cell-invasion analysis, the cells were incubated with 100 mM of EGCG for 2 hours. The cells were then added into a Matrigel-coated Cell Insert. After incubation at 37 degrees C for 24 hours, the cells visible through the Matrigel were counted under the microscope. All human biliary tract cancer cells studied showed a significant suppression of cell growth by EGCG treatment in a dose-dependent manner (27.2%, 16.0%, and 10.1%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at the dose of 200 mM). Epigallocatechin-3-gallate treatment also produced a significant suppression of invasive ability of the carcinoma cells (12.6%, 11.2%, 7.9%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at a dose of 100 mM). These data indicated that EGCG might be a potent biological inhibitor of human biliary tract cancers, reducing their proliferative and invasive activities.





Volume 118, Issue 7, Pages 1635-1644 (April 2006)

Rodriguez SK, Guo W, Liu L, Band MA, Paulson EK, Meydani M.

Green tea catechin, epigallocatechin-3-gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex.

Vascular Biology Laboratory, JM USDAHumanNutritionCenter on Aging at TuftsUniversity, Boston, USA.

A potential mechanism by which green tea may prevent cancer development is through the inhibition of angiogenesis. We have shown previously that the green tea catechin, epigallocatechin gallate (EGCG), inhibits endothelial cell tube formation through the inhibition of vascular endothelial growth factor (VEGF)-induced Akt activation and vascular endothelial (VE)-cadherin phosphorylation. Furthermore, EGCG can suppress oxidant-induced production of the proangiogenic cytokine interleukin (IL)-8. To further elucidate the antiangiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGF-induced signaling in human umbilical vein endothelial cells (HUVECs). We show that EGCG at physiological doses (0.5-10 microM) markedly inhibits the formation of a vascular endothelial growth factor receptor 2 complex formed upon the binding of its ligand VEGF. This disruption results in a significant and dose-dependent decrease in PI3-kinase activity. Electrophoretic mobility shift assay revealed that EGCG decreased the PI3 kinase-dependent activation and DNA-binding ability of NF-kappaB, likely acting through decreasing phosphorylation and degradation of IkappaB. VEGF-induced IL-8 production at the mRNA (real time RT-PCR) and protein levels (ELISA) are also suppressed with EGCG. These results suggest a novel mechanism for green tea's anticancer effects where EGCG can abrogate VEGF signaling by interfering with the formation of a receptor complex, resulting in attenuated mitogenic and angiogenic signaling.


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Volume 62, Issue 4, Pages 765-771 (October 2002)


Kazi A, Smith DM, Zhong Q, Dou QP.


Inhibition of bcl-x(l) phosphorylation by tea polyphenols or epigallocatechin-3-gallate is associated with prostate cancer cell apoptosis.

Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.

Prostate cancer cells demonstrate slow growth kinetics and chemoresistance. Tea polyphenols have been shown to exert prostate cancer-preventative effects. Here we report that growth-arrested prostate cancer cells expressed high levels of a hyperphosphorylated Bcl-X(L) in mitochondria. Treatment with tea polyphenols or the major tea component epigallocatechin-3-gallate blocked expression of the hyper-, but not hypophosphorylated Bcl-X(L) in mitochondria, accompanied by cytochromec release, caspase activation, and apoptosis. Studies using specific inhibitors suggest that tea inhibits p38 mitogen-activated protein kinase and the proteasome activities, leading to inhibition of Bcl-X(L) phosphorylation and induction of prostate cancer cell death.







Oxford University Press




Volume 23, Number 9, Pages 1497-1503 (September 2002)


Sun CL, Yuan JM, Lee MJ, Yang CS, Gao YT, Ross RK, Yu MC.


Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China.

NorrisComprehensiveCancerCenter, University of Southern California Keck School of Medicine, Los Angeles, USA.

Experimental studies have shown that tea and tea polyphenols have anticarcinogenic properties. There have been no prospective investigations examining the relationship between tea polyphenols and cancer risk using validated biomarkers. In the present study, a nested case-control study design was used to investigate the association between prediagnostic urinary tea polyphenol markers and subsequent risk of gastric and esophageal cancers. One hundred and ninety incident cases of gastric cancer and 42 cases of esophageal cancer occurring in members of the Shanghai Cohort (18 244 men aged 45-64 years at recruitment with up to 12 years of follow-up) were compared with 772 cohort control subjects. The control subjects were individually matched to the index cases by age, month and year of sample collection, and neighborhood of residence (case-control ratio = 1:3 for gastric cancer, 1:5 for esophageal cancer). Urinary tea polyphenols, including epigallocatechin (EGC) and epicatechin (EC), and their respective metabolites 5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), were measured in all study subjects by means of a validated assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models. After exclusion of cases diagnosed under 4 years follow-up, urinary EGC positivity showed a statistically significant inverse association with gastric cancer (OR = 0.52, 95% CI = 0.28-0.97) after adjustment for Helicobactor pylori seropositivity, smoking, alcohol drinking, and level of serum carotenes. The protective effect was primarily seen among subjects with low (below population median) serum carotenes. The odds ratio for EGC positivity was 0.49 (95% CI = 0.26-0.94) among subjects with low serum carotenes while the corresponding odds ratio among subjects with higher levels of serum carotenes was 1.02 (95% CI = 0.46-2.28). Similar tea polyphenol-cancer risk associations were observed when the gastric cancer and esophageal cancer sites were combined. The present study provides direct evidence that tea polyphenols may act as chemopreventive agents against gastric and esophageal cancer development.

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