Inhibition of lung carcinogenesis and effects on angiogenesis and apoptosis in A/J mice by oral administration of green tea.
Oral administration of tea (Camellia sinensis) has been shown to inhibit the formation and growth of several tumor types in animal models. The present study investigated the effects of treatment with different concentrations of green tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Two days after a single dose of NNK (100 mg/kg body weight, i.p.), the mice were given 0.1, 0.2, 0.4, and 0.6% green tea solution (1, 2, 4, and 6 g of tea solids, respectively, dissolved in 1 l of water), 0.02% caffeine, or water as the sole source of drinking fluid until the termination of the experiment. Only the treatment with 0.6% tea preparation significantly reduced lung tumor multiplicity (mean +/- SE, 6.07 +/- 0.77 vs. 8.60 +/- 0.50 tumors per mouse, P = 0.018). Treatment with 0.6% tea also inhibited angiogenesis, as indicated by the lower microvessel density (number of blood vessels/mm2) based on immunostaining for the von Willebrand factor antigen (81.9 +/- 9.5 vs. 129.4 +/- 8.2, P = 0.0018) and anti-CD31 antibody staining (465.3 +/- 61.4 vs. 657.1 +/- 43.6, P = 0.0012). Signif-icantly lower vascular endothelial growth factor immunostaining scores were also observed in the 0.6% tea-treated group (0.98 +/- 0.17 vs. 1.43 +/- 0.07, P = 0.006). The apoptosis index was significantly higher in lung adenomas from 0.6% tea-treated mice based on morphological analysis of cell apoptosis (2.51 +/- 0.18% vs. 1.57 +/- 0.11%, P = 0.00005), and the result was further confirmed using the TUNEL method. Inhibition of angiogenesis and the induction of apoptosis by green tea may be closely related to the inhibition of pulmonary carcinogenesis.
Nutr Cancer. 2004;48(1):44-53
Update on chemoprevention of prostate cancer.
PURPOSE OF REVIEW: Prostate cancer remains the most commonly diagnosed visceral cancer in men in the United States, with almost 200,000 newly diagnosed cases in 2003. Prevention of this disease would have a major impact on disease-associated cost, morbidity, and mortality for a large segment of the population. A major advance in prevention of prostate cancer came in 2003 with the publication of the Prostate Cancer Prevention Trial. This overview summarizes the results of that trial, the design of other large-scale trials, and advances in understanding of the molecular mechanisms underlying the effect of other promising agents. RECENT FINDINGS: The Prostate Cancer Prevention Trial demonstrated that use of finasteride is associated with a 25% reduction in the 7-year period prevalence of prostate cancer in men over age 55 years with normal digital rectal exam and initial prostate specific antigen <3.0 ng/ml. Use of finasteride was associated with a slightly higher risk of Gleason sum 7-10 tumors, some sexual side effects, and fewer urinary symptoms. A substantial body of new molecular evidence supports the existing body of clinical and epidemiological data leading to testing of vitamin E and selenium as preventative agents in men at risk for prostate cancer. Epidemiologic and molecular evidence also makes cyclooxygenase-2 inhibitors, lycopene, soy, and green tea promising agents. SUMMARY: Results of a population-based, randomized phase III trial demonstrates that finasteride can prevent prostate cancer. A large amount of data supports the use of other agents as potential preventatives, including selenium, vitamin E, vitamin D, other 5-alpha-reductase inhibitors, cyclooxygenase-2 inhibitors, lycopene, and green tea. Some of these agents are being tested in new large-scale phase III clinical trials.
Curr Opin Urol. 2004 May;14(3):143-9
EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis.
Telomerase is elevated in >90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Dietary components that are capable of inhibiting the growth of cancer cells without affecting the growth of normal cells are receiving considerable attention in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here, we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive or colony forming potential, and also decreased cell viability at different time points studied (approximately 80% inhibition) in human breast carcinoma MCF-7 cells but had no adverse effect on the growth of normal mammary cells. Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%). In order to identify the possible mechanism of decreased cell viability and induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%), and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit of telomerase. Additional studies demonstrated that EGCG also inhibited the protein expression of hTERT, which indicated that inhibition of telomerase was associated with down-regulation of hTERT. Together, our results indicate that EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to the suppression of cell viability and induction of apoptosis, thus providing the molecular basis for the development of EGCG as a novel chemopreventive and pharmacologically safe agent against breast cancer.
Int J Oncol. 2004 Mar;24(3):703-10
HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking.
Human T-cell lymphotropic virus type 1 (HTLV-1) is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV-1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV-1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34-40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV-1-infected T-cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV-1 provirus load in peripheral blood lymphocytes on HTLV-1 carriers. We recruited 83 asymptomatic HTLV-1 carriers to examine HTLV-1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty-seven subjects were followed up for 5 months by measuring HTLV-1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real-time PCR quantification of HTLV-1 DNA revealed a wide range of variation of HTLV-1 provirus load among asymptomatic HTLV-1 carriers (0.2-200.2 copies of HTLV-1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV-1 provirus load as compared with the controls (P = 0.031). These results suggest that green tea drinking suppresses proliferation of HTLV-1-infected lymphocytes in vivo.
Cancer Sci. 2004 Jul;95(7):596-601
Green and black teas inhibit atherosclerosis by lipid, antioxidant, and fibrinolytic mechanisms.
Tea is the most widely consumed beverage in the world, second only to water. Most laypersons and scientists believe that green tea is healthier than black tea due to the low incidence of heart disease and cancer in the Orient. Here, we report the first dose-response comparison of a green and black tea on normal hamsters after long-term supplementation and on a hamster model of atherosclerosis. Both teas were equally effective in inhibiting atherosclerosis with the lower dose decreasing it 26-46% and the high dose decreasing it 48-63%. Athero-sclerosis was inhibited by three mechanisms: hypolipemic, antioxidant, and antifibrinolytic. There was a significant correlation between atherosclerosis and the three mechanisms. In the normal animals, teas also caused some improvement in plasma low density lipoprotein (LDL), LDL/high density lipoprotein ratio, triglycerides, lipid peroxides, lower density lipoprotein lipid peroxides, and fibrinogen. Isolated lower density lipoprotein oxidizability was also reduced in all groups. Green and black teas were equally effective at human equivalent doses, thus confirming human intervention and epidemiology studies and providing mechanisms for teas’ benefit.
J Agric Food Chem. 2004 Jun 2;52(11):3661-5
Effects of green tea intake on the development of coronary artery disease.
BACKGROUND: Green tea, a popular beverage in Japan, contains many polyphenolic antioxidants, which might prevent atherosclerosis. This study was designed to determine whether the consumption of green tea is proportionately associated with a decreased incidence of coronary artery disease (CAD) and the cardiovascular and cerebrovascular prognosis. METHODS AND RESULTS: The study group comprised 203 patients who underwent coronary angiography (109 patients with significant coronary stenosis and 94 patients without). Predictors for CAD were analyzed and the patients’ cardiovascular and cerebrovascular events were followed. Green tea consumption was significantly higher in patients without CAD than in those with CAD (5.9+/-0.5 vs 3.5+/-0.3 cups/day; p<0.001). An inverse relationship between the intake of green tea and the incidence of CAD was observed (p<0.001). The green tea intake per day was an independent predictor for CAD based on a multivariate logistic regression analysis (odds ratio: 0.84 and 95% confidence interval: 0.76-0.91). In contrast, the green tea intake was not a predictor of cardiovascular and cerebrovascular events based on the Cox proportional hazard model. CONCLUSIONS: Green tea consumption was associated with a lower incidence of CAD in the present study population in Japan. Therefore, the more green tea patients consume, the less likely they are to have CAD.
Circ J. 2004 Jul;68(7):665-70
Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice.
BACKGROUND: Oxidative stress has been implicated in vascular injury and atherogenesis, and antioxidant treatment has shown favorable results in preclinical studies. Despite this, antioxidant therapy has failed to show benefit in clinical trials. Failure of antioxidants in clinical trials may be partly because such therapy is started after atherosclerosis is already well established, whereas the benefits in animal models may be results from early initiation of antioxidants while atherosclerosis is still evolving. METHODS AND RESULTS: To test this hypothesis, we evaluated the effect of epigallocatechin gallate (EGCG), the main antioxidant derived from green tea, on evolving and established atherosclerotic lesions in hypercholesterolemic apolipoprotein E-null mice. Established native aortic atherosclerotic lesions and evolving atherosclerotic lesions produced by periadventitial cuff injury to carotid arteries were assessed in mice after 21 and 42 days of treatment with daily intraperitoneal injections of EGCG (10 mg/kg) or PBS. EGCG treatment resulted in an increase in the antioxidant capacity in local vascular tissue and systemic circulation and reduced vascular smooth muscle cell proliferation and redox-sensitive gene activation in vitro. EGCG reduced cuff-induced evolving atherosclerotic plaque size at 21 and 42 days by 55% and 73%, respectively, compared with PBS treatment (P<0.05). Conversely, EGCG had no effect on established lesions in the aortic sinuses or the rest of the aorta. CONCLUSIONS: Our data suggest that antioxidant EGCG differentially reduces evolving atherosclerotic lesions without influencing established atherosclerosis in the apolipoprotein E-null mice.
Circulation. 2004 May 25;109(20):2448-53