Effect of Green Tea Extract on the Induction of Ornithine Decarboxylase and   the Activation of Extracellular Signal-Regulated Kinase in Bladder Carcinoma   ECV304 Cells.

Nutr Cancer. 2003;47(1):104-10.

Facchini A, Zanella B, Stefanelli C, Guarnieri C, Flamigni   F.

Dipartimento di Biochimica "G. Moruzzi," Universita di Bologna.

According to several studies, green tea and individual catechins   can inhibit the induction of ornithine decarboxylase (ODC), the key enzyme in   the biosynthesis of polyamines. It has been suggested that the inhibition of   ODC induction may offer an explanation to the anticancer and chemopreventive   activities of green tea. In the present study, however, treatment of bladder   carcinoma ECV304 cells with green tea extract (GTE) was not able to reduce the   induction of ODC by fetal calf serum. Actually, in the absence of serum, GTE   provoked a dose-dependent and remarkable induction of ODC activity. The induction   of ODC, which could be elicited also by (-)-epigallocatechin 3-gallate, a major   green tea component, required an early activation of extracellular signal-regulated   kinase 1 and 2 (ERK), and both events appeared to be dependent on an alteration   of the status of cellular thiol groups. Pretreatment with specific ERK or ODC   inhibitors was able to prevent a late caspase activation but hardly affected   the loss of cell viability provoked by GTE. In conclusion, to our knowledge,   this is the first study showing that GTE can promote ODC induction in a tumor   cell line.

PMID: 14769544 [PubMed - in process]

Tea beverage in chemoprevention of prostate cancer: a mini-review.

Nutr Cancer. 2003;47(1):13-23.

Saleem M, Adhami VM, Siddiqui IA, Mukhtar H.

Department of Dermatology, University of Wisconsin, Madison, WI.

Because prostate cancer has a long latency period and is typically   diagnosed in elderly men, it represents an ideal candidate disease for chemoprevention.   Therefore, even a modest delay achieved through intervention could have a significant   impact on the outcome of this disease. Epidemiological and laboratory studies   have provided convincing evidence that diet, genetic factors, and lifestyle   are major causes of prostate cancer. Although surgery, radiotherapy, and hormone   therapy are the most widely accepted curative options for a selected group of   patients suffering from prostate cancer, the side effects of these treatments   are many. In recent years, many dietary agents have been being described that   show a wide range of chemopreventive effects in cell culture and selected animal   model systems of prostate carcinogenesis. One such agent is the beverage tea,   which, next to water, is the most popularly consumed beverage in the world.   The epidemiological studies and recent data, amassed from various laboratories   around the world, provide evidence that tea polyphenols such as epigallocatechin-3-gallate,   epigallocatechin, and epicatechin-3-gallate may have the potential to lower   the risk of prostate cancer in the human population. Recently, it has been shown   that green tea polyphenols, when given to TRAMP, a transgenic mouse model that   mimics progressive forms of human prostate cancer, exert remarkable preventive   effects against prostate cancer development. Chemoprevention of prostate cancer   by tea polyphenols appears to occur through the modulation of various molecular   targets. This article attempts to address the issue of the possible use of tea,   especially green tea, for the chemoprevention of prostate cancer.

PMID: 14769533 [PubMed - in process]

Successful storage of peripheral nerve before transplantation   using green tea polyphenol: an experimental study in rats.

Exp Neurol. 2003 Dec;184(2):688-96.

Ikeguchi R, Kakinoki R, Okamoto T, Matsumoto T, Hyon   SH, Nakamura T.

Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University,   Kyoto 606-8507, Japan.

Green tea polyphenol is known to act as a buffer, reducing biological   responses to oxidative stress. Several effects of polyphenol have been reported,   such as protection of tissue from ischemia, antineoplasmic and anti-inflammatory   effects, and suppression of arteriosclerosis. In this study, we investigated   whether peripheral nerve segments could be kept viable in a polyphenol solution   for 1 month. Sciatic nerve segments, 20 mm long, were harvested from Lewis rats   and treated in three different ways before transplanting to recipient Lewis   rats to bridge sciatic nerve gaps created by removal of 15-mm-long nerve segments.   Group F: nerve segments were transplanted immediately after harvesting. Group   P: nerve segments were transplanted after they had been stored in Dulbecco's   Modified Eagle's Medium (DMEM) containing polyphenol for 7 days at 4 degrees   C and then in DMEM for 21 days at 4 degrees C. Group M: nerve segments were   stored in DMEM solution alone for 28 days at 4 degrees C. Viability of the nerve   segments was assessed by vital staining (calcein-AM/ethidium homodimer), by   electron microscopy and by genomic studies before transplantation. Nerve regeneration   was evaluated using electrophysiological and morphological studies 12 and 24   weeks after transplantation. Neural cell viability of the preserved nerve segments   was confirmed in group P, in which the nerve regeneration was similar to that   in group F and superior to that in group M. Peripheral nerve segments can be   successfully preserved for 1 month using green tea polyphenol.

PMID: 14769360 [PubMed - in process]

Inhibitory effects of autoimmune disease by green tea in MRL-Faslprcg/Faslprcg   mice.

In Vivo. 2003 Nov-Dec;17(6):545-52.

Sayama K, Oguni I, Tsubura A, Tanaka S, Matsuzawa A.

Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka   University, 836 Ohya, Shizuoka-shi 422-8529, Japan. acksaya@agr.shizuoka.ac.jp

To investigate whether green tea has inhibitory effects on the   development of autoimmune disease (AID), one-month-old MRL-Faslprcg/Faslprcg   mice were fed diets containing 2% green tea powder (GTP) for 3 months. At the   end of GTP feeding, the weights of body, subcutaneous (s.c.) and intraperitoneal   (i.p.) lymph nodes (LN), kidneys, spleen and intraperitoneal adipose tissue   (IPAT), serological abnormalities and renal lesions were compared between GTP-fed   and control mice. SCLN, IPLN, kidneys and IPAT weights in both sexes, spleen   weight in males and body weight increase in males were significantly lower in   GTP-fed mice. Particularly, LN hyperplasia and fatty accumulation were markedly   reduced by GTP. Serum levels of anti-DNA antibodies and immune complexes (IC)   were significantly lowered and proteinuria and blood urea nitrogen tended to   be improved by GTP. The incidence of serious glomerulonephritis was significantly   lower and nephric vasculitis was almost completely prevented in GTP-fed mice.   Moreover, the survival of mice was significantly prolonged by GTP feeding for   6 months. These results indicate that the progression of lupus-like syndrome   including glomerulonephritis was significantly delayed by reduced production   of autoantibodies and IC in GTP-fed MRL-Faslprcg/Faslprcg mice, which led to   the prolonged survival.

PMID: 14758719 [PubMed - in process]

Green tea polyphenol (-)-epigallocatechin-3-gallate protects   rat PC12 cells from apoptosis induced by serum withdrawal independent of P13-Akt   pathway.

Neurotox Res. 2003;5(6):419-24.

Mandel S, Reznichenko L, Amit T, Youdim MB.

Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative   Diseases Research, Technion-Faculty of Medicine, Haifa 31096, Israel.

Our recent studies have demonstrated that green tea polyphenol   (-)-epigallocatechin-3-gallate (EGCG) exerts neuroprotective/neurorescue effects   against B-amyloid toxicity and protects neuronal cells from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium   ion (MPP+) and 6-hydroxydopamine in vitro, or from N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-   (MPTP-) induced nigral dopaminergic neuronal loss in mice. In the present study,   we report that EGCG (0.1 and 1 microM) significantly protects rat pheochromocytoma   PC12 cells from apoptosis induced by serum support withdrawal, suggesting that   EGCG may play a role in the growth of PC12 cells, where it stimulates survival-promoting   pathways.

PMID: 14715445 [PubMed - indexed for MEDLINE]

Green tea extract suppresses the age-related increase   in collagen crosslinking and fluorescent products in C57BL/6 mice.

Int J Vitam Nutr Res. 2003 Nov;73(6):453-60.

Rutter K, Sell DR, Fraser N, Obrenovich M, Zito M, Starke-Reed   P, Monnier VM.

Yorktown High School, Arlington, VA 22207, USA.

Collagen crosslinking during aging in part results from Maillard   reaction endproducts of glucose and oxoaldehydes. Because of the tight link   between oxidative and carbonyl stress, we hypothesized that natural antioxidants   and "nutriceuticals" could block collagen aging in C57BL/6 mice. Six   groups of young and adult mice received vitamin C, vitamin E, vitamin C&E,   blueberry, green tea extract (GTE), or no treatment for a period of 14 weeks.   Body weights and collagen glycation were unaltered by the treatment. However,   GTE or vitamin C&E combined blocked tendon crosslinking at 10 months of   age (p < 0.05, adult group). GTE also blocked fluorescent products at 385   and 440 nm (p = 0.052 and < 0.05, respectively) and tended to decrease skin   pentosidine levels. These results suggest that green tea is able to delay collagen   aging by an antioxidant mechanism that is in part duplicated by the combination   of vitamin C and E.

PMID: 14743550 [PubMed - in process]

Modulation of phosphatidylinositol-3-kinase/protein kinase   B- and mitogen-activated protein kinase-pathways by tea polyphenols in human   prostate cancer cells.

J Cell Biochem. 2004 Feb 1;91(2):232-42.

Siddiqui IA, Adhami VM, Afaq F, Ahmad N, Mukhtar H.

Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706.

We have earlier shown that oral infusion of a polyphenolic fraction   isolated from green tea, at a human achievable dose (equivalent to six cups   of green tea per day), significantly inhibits prostate cancer (PCA) development   and metastasis in transgenic adenocarcinoma of mouse prostate (TRAMP) model   that closely mimics progressive form of human prostatic disease (Gupta et al.   [2001]: Proc. Natl. Acad. Sci. U.S.A. 98:10350-10355.). A complete understanding   of the mechanism(s) and molecular targets of PCA chemopreventive effects of   tea polyphenols may be useful in developing novel approaches for its prevention.   In this study, we employed two distinct human PCA cell lines viz. DU145 (androgen-unresponsive   prostate carcinoma cells) and LNCaP (androgen-responsive prostate carcinoma   cells) and, employing immunoblot analysis, we evaluated the effect of epigallocatechin-3-gallate   (EGCG), the major polyphenol present in green tea and theaflavins (TF), the   major polyphenol present in black tea on phosphatidylinositol-3-kinase (PI3K)/protein   kinase B (PKB) and mitogen-activated protein kinase (MAPK) pathways. Both EGCG   and TF treatment were found to (i) decrease the levels of PI3K and phospho-Akt   and (ii) increase Erk1/2 in both DU145 and LNCaP cells. Our data showing the   inhibition of the constitutive levels of PI3K and the phosphorylation of Akt   could be important because the treatment approaches should be aimed at the inhibition   of the constitutive levels of PI3K and Akt. Our data also suggest that Erk1/2   could be involved in the anti-cancer effects of EGCG and TF. Taken together,   our study, for the first time demonstrated the modulation of the constitutive   activation of PI3K/Akt and Erk1/2 pathways by EGCG as well as TF. We suggest   that detailed studies in appropriate tumor model system are needed to establish   the relevance of the cell culture work to in vivo models. Copyright 2003 Wiley-Liss,   Inc.

PMID: 14743383 [PubMed - in process]

Higher consumption of green tea may enhance equol production.

Asian Pac J Cancer Prev. 2003 Aug-Dec;4(4):297-301.

Miyanaga N, Akaza H, Takashima N, Nagata Y, Sonoda T,   Mori M, Naito S, Hirao Y, Tsukamoto T, Fujioka T.

Department of Urology, Post-graduate University of Tsukuba, Ibaraki, 305-8575,   Japan. akazah@md.tsukuba.ac.jp

BACKGROUND: Our previous case-control study revealed that Japanese   living in Japan and Koreans living in Korea can be divided into equol producers   who have an ability to metabolize daidzein to equol and non-producers, and that   the incidence of prostate cancer is higher in the latter group. In the present   study, we examined relationships between type of food intake and the capacity   for equol production in Japanese subjects. METHODS: The subjects were the individuals   analyzed for the ability to produce equol in our previous study and newly registered   cases. From December 2000 to December 2002, 276 hospitalized patients were interviewed   face-to-face and blood samples were collected before breakfast. These included   122 patients with prostate cancer and 154 age-matched controls. RESULTS: The   frequency of equol producers (0.5 ng/ml or more) among cases and controls was   29% and 45%, respectively (p = 0.004). The consumption of soybeans and green   tea were significantly higher in equol producers than in the non-producers (p<0.05).   By contrast, the consumption of selenium and fiber was significantly lower in   equol producers (p<0.05). CONCLUSIONS: Our results suggest that higher consumption   of soybean and green tea are strongly related to the establishment of a capacity   for equol production.

PMID: 14728586 [PubMed - in process]

Black and green tea polyphenols attenuate blood pressure   increases in stroke-prone spontaneously hypertensive rats.

J Nutr. 2004 Jan;134(1):38-42.

Negishi H, Xu JW, Ikeda K, Njelekela M, Nara Y, Yamori   Y.

College of Human Life and Environment, Kinjo Gakuin University, Nagoya 463-8521,   Japan. pnm@apricot.ocn.ne.jp

Oxidative stress was reported to be involved not only in cardiovascular   diseases, but also in hypertension. Epidemiologic studies indicated that tea   consumption slightly reduces blood pressure. We conducted two studies to determine   whether black and green tea can lower blood pressure (BP) in stroke-prone spontaneously   hypertensive rats (SHRSP). Male SHRSP (n=15) were allowed to recover for 2 wk   after a transmitter for measuring BP was implanted in the peritoneal cavity.   The rats were divided into three groups: the control group consumed tap water   (30 mL/d); the black tea polyphenol group (BTP) consumed water containing 3.5   g/L thearubigins, 0.6 g/L theaflavins, 0.5 g/L flavonols and 0.4 g/L catechins;   and the green tea polyphenol group (GTP) consumed water containing 3.5 g/L catechins,   0.5 g/L flavonols and 1 g/L polymetric flavonoids. The telemetry system was   used to measure BP, which were recorded continuously every 5 min for 24 h. During   the daytime, systolic and diastolic BP were significantly lower in the BTP and   GTP groups than in the controls. Protein expressions of catalase and phosphorylated   myosin light chain (MLC-p) were measured in the aorta by Western blotting. GTP   significantly increased catalase expression, and BTP and GTP significantly decreased   MLC-p expression in the aorta. These data demonstrate that both black and green   tea polyphenols attenuate blood pressure increases through their antioxidant   properties in SHRSP. Furthermore, because the amounts of polyphenols used in   this experiment correspond to those in approximately 1 L of tea, the regular   consumption of black and green tea may also provide some protection against   hypertension in humans.

PMID: 14704290 [PubMed - in process]

Protective effects of green tea polyphenol against reactive   oxygen species-induced oxidative stress in cultured rat calvarial osteoblast.

Cell Biol Toxicol. 2003 Oct;19(5):325-37.

Park YH, Han DW, Suh H, Ryu GH, Hyon SH, Cho BK, Park   JC.

Department of Medical Engineering, Cardiovascular Research Institute, Yonsei   University College of Medicine Seoul, Korea.

The injurious effects of reactive oxygen species on osteoblasts   and the potential protective role played by green tea polyphenols (GtPP) were   investigated using primarily cultured rat calvarial osteoblasts. Oxidative stress   was induced in cultured osteoblasts, either by adding 100 mmol/L H2O2 or by   the action of 40 U/L xanthine oxidase (XO) in the presence of xanthine (250   micromol/L). After incubation, the cellular viability, function and morphology   were evaluated. Both treatments produced a significant reduction in osteoblast   viability, as assessed by a two-colored fluorescence staining method combined   with flow cytometric analysis and MTT assay. A significant reduction in the   alkaline phosphatase activity was observed after H2O2 addition, whereas XO did   not have the same effect. On the microscopic observations, the morphological   changes and intracellular ultrastructural damages were remarkably induced by   both treatments. The H2O2-induced alterations were prevented by pre-incubating   the osteoblasts with 200 microg/ml GtPP for 1 h. When the oxidative stress was   induced by XO, the cellular viability and morphology was also maintained at   the same polyphenol concentration. These results demonstrate that GtPP can act   as a biological antioxidant in a cell culture experimental model and protect   cells from oxidative stress-induced toxicity.

PMID: 14703119 [PubMed - in process]

Epigallocatechin-3-gallate inhibits epidermal growth   factor receptor signaling pathway: evidence for direct inhibition of ERK1/2   and AKT kinases.

J Biol Chem. 2003 Dec 29 [Epub ahead of print]

Sah JF, Balasubramanian S, Eckert RL, Rorke EA.

Environmental Health Sciences, Case Western Reserve University, Cleveland,   OH 44106.

Epidermal growth factor receptor (EGFR) activation is absolutely   required for cervical cell proliferation. This suggests that EGFR-inhibitory   agents may be of therapeutic value. In the present study, we investigate the   effects of epigallocatechin-3-gallate (EGCG), a bioactive green tea polyphenol,   on EGFR signaling in cervical cells. EGCG inhibits epidermal growth factor (EGF)-dependent   activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein   kinases, ERK1/2 and p38. EGCG also inhibits EGFR-dependent AKT activity. The   EGCG-dependent reduction in ERK and AKT activity is associated with reduced   phosphorylation of downstream substrates, including p90RSK, FKHR and BAD. These   changes are associated with increased p53, p21WAF-1 and p27KIP-1 level, reduced   cyclin E level, and reduced cdk2 kinase activity. Consistent with these findings,   flow cytometry and TUNEL staining reveal EGCG-dependent G1 arrest. Moreover,   sustained EGCG treatment causes apoptotic cell death. In addition to inhibiting   EGFR, cell free studies demonstrate that EGCG directly inhibits ERK1/2 and AKT,   suggesting that EGCG simultaneously acts at multiple levels to inhibit EGF-dependent   signaling. Importantly, the EGCG inhibition is selective, as EGCG does not effect   the EGFR-dependent activation of JNK. These results suggest that EGCG acts to   selectively inhibit multiple EGF-dependent kinases to inhibit cell proliferation.

PMID: 14701854 [PubMed - as supplied by publisher]

Epigallocatechin 3-gallate attenuates neuronal damage   induced by 3-hydroxykynurenine.

Toxicology. 2004 Jan 15;195(1):53-60.

Jeong JH, Kim HJ, Lee TJ, Kim MK, Park ES, Choi BS.

Department of Pathology, Medical School, Chung Ang University, 221 Heuksuk-Dong,   Dongjak-Gu, Seoul 156-756, South Korea.

3-Hydroxykynurenine (3-HK), which is an endogenous metabolite   of tryptophan in the kynurenine pathway, is a potential neurotoxin in several   neurodegenerative disorders. Epigallocatechin 3-gallate (EGCG), a major compound   of green tea, is recognized as a promising natural substance for protection   against neuronal diseases. This study investigated the possible protective roles   and mechanism of EGCG, against 3-HK-induced cell death. It was found that 3-HK   induces neuronal cell death in the human neuroblastoma SH-SY5Y cell line. The   reduced cell viability produced characteristic features such as cell shrinkages,   plasma membrane blebbing, chromatin condensation, and nuclear fragmentation.   The cells treated with 3-HK showed an increase in the concentration of reactive   oxygen species (ROS) as well as in caspase activity. In addition, both are involved   in the 3-HK-induced apoptosis. EGCG attenuated the cell viability reduction   by 3-HK in both a dose- and time-dependent manner. Optical microscopy showed   that EGCG inhibited the cell morphological features in the 3-HK-treated cells.   Furthermore, the increase in the ROS concentration and the caspase activities   by 3-HK were also attenuated by EGCG. These results showed that EGCG has a protective   effect on the 3-HK induced cell death by inhibiting ROS production and caspase   activity. The results suggest that EGCG might be a promising protective substance   against the neuronal degenerative diseases.

PMID: 14698567 [PubMed - in process]

Effects of green tea and high-fat diet on arachidonic acid metabolism and aberrant   crypt foci formation in an azoxymethane-induced colon carcinogenesis mouse model.

Nutr Cancer. 2003;46(2):172-8.

Ju J, Liu Y, Hong J, Huang MT, Conney AH, Yang CS.

Graduate Program of Food Science, Rutgers, the State University of New Jersey,   New Brunswick, NJ 08854, USA.

Excessive fat consumption is a risk factor for colon carcinogenesis,   and green tea consumption may reduce the risk of colon and other cancers. The   current study was designed to investigate the effects of green tea and a high-fat   diet on arachidonic acid metabolism and aberrant crypt foci formation in an   azoxymethane (AOM)-induced colon carcinogenesis mouse model. We also determined   whether green tea consumption altered the size of regional fat pads. CF-1 female   mice were maintained on either a high-fat (20% corn oil) or a low-fat (5% corn   oil) diet. AOM was given subcutaneous at a dose of 7.5 mg/kg body weight at   6 wk and then a dose of 10 mg/kg at 7 wk of age. Two weeks after the second   AOM injection, 0.6% green tea (6 mg tea solids/ml) was given as the drinking   fluid and continued for 10 wk until the experiment was terminated. In the AOM-treated   mice not receiving green tea, the high-fat diet significantly enhanced colonic   levels of 5-lipoxygenase, leukotriene A4 hydrolase, and leukotriene B4, but   it did not significantly alter prostaglandin E2 levels and aberrant crypt foci   formation. In AOM-treated mice on the high-fat diet, green tea significantly   decreased colonic levels of cytosolic phospholipase A2, 5-lipoxygenase, and   leukotriene B4; green tea treatment also decreased the number of aberrant crypt   foci (P < 0.05). The weights of parametrial and retroperitoneal fat pads   were increased by the high-fat diet and decreased by green tea treatment. The   current results indicate that green tea consumption and dietary fat modulate   5-lipoxygenase-dependent pathway of arachidonic acid metabolism during AOM-induced   colon carcinogenesis. Green tea inhibits ACF formation in mice on a high corn   oil diet, suggesting its possible inhibitory effect on colon carcinogenesis   in populations such as those in Western countries that consume high amounts   of fat.

PMID: 14690793 [PubMed - in process]

Cancer prevention by tea polyphenols is linked to their   direct inhibition of antiapoptotic Bcl-2-family proteins.

Cancer Res. 2003 Dec 1;63(23):8118-21.

Leone M, Zhai D, Sareth S, Kitada S, Reed JC, Pellecchia   M.

The Burnham Institute, La Jolla, California 92037, USA.

Epidemiological data and in vitro studies on cancer chemoprevention   by tea polyphenols have gained attention recently from the scientific community,   nutritionists, the pharmaceutical industry, and the public. Despite the several   efforts made recently to elucidate the molecular basis for the anticancer activity   of these natural products, little correlation has been found thus far between   the putative protein targets of compounds found in tea extracts and levels found   in plasma after tea consumption. Here, by using a combination of nuclear magnetic   resonance binding assays, fluorescence polarization assay, and computational   docking studies, we found that certain green tea catechins and black tea theaflavins   are very potent inhibitors (K(i) in the nanomolar range) of the antiapoptotic   Bcl-2-family proteins, Bcl-x(L) and Bcl-2. These data suggest a strong link   between the anticancer activities of these tea polyphenols and their inhibition   of a crucial antiapoptotic pathway, which is implicated in the development of   many human malignancies.

PMID: 14678963 [PubMed - in process]

Essential role of caspases in epigallocatechin-3-gallate-mediated   inhibition of nuclear factor kappaB and induction of apoptosis.

Oncogene. 2003 Dec 15 [Epub ahead of print]

Gupta S, Hastak K, Afaq F, Ahmad N, Mukhtar H.

Department of Urology, Case Western Reserve University, Cleveland, OH 44106,   USA.

Green tea constituent (-) epigallocatechin-3-gallate (EGCG)   has shown remarkable cancer-preventive and some cancer-therapeutic effects.   This is partially because of its ability to induce apoptosis in cancer cells   without affecting normal cells. Previous studies from our laboratory have shown   the involvement of NF-kappaB pathway in EGCG-mediated cell-cycle deregulation   and apoptosis of human epidermoid carcinoma A431 cells. Here we show the essential   role of caspases in EGCG-mediated inhibition of NF-kappaB and its subsequent   apoptosis. Treatment of A431 cells with EGCG (10-40 microg/ml) resulted in dose-dependent   inhibition of NF-kappaB/p65, induction of DNA breaks, cleavage of poly(ADP-ribose)   polymerase (PARP) and morphological changes consistent with apoptosis. EGCG   treatment of cells also resulted in significant activation of caspases, as shown   by the dose- and time-dependent increase in DEVDase activity, and protein expression   of caspase-3, -8 and -9. EGCG-mediated caspase activation induces proteolytic   cleavage of NF-kappaB/p65 subunit, leading to the loss of transactivation domains,   and driving the cells towards apoptosis. EGCG-mediated induction of apoptosis   was significantly blocked by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone   (Z-VAD-FMK), and moderately blocked by the specific caspase-3 inhibitor Z-DEVD-FMK.   Further, pretreatment of cells with Z-VAD-FMK was found to suppress the cleavage   of NF-kappaB/p65 subunit, thereby increasing nuclear translocation, DNA binding   and transcriptional activity, thus protecting the cells from EGCG-induced apoptosis.   Taken together, these studies for the first time demonstrate that EGCG-mediated   activation of caspases is critical, at least in part, for inhibition of NF-kappaB   and subsequent apoptosis.Oncogene advance online publication, 15 December 2003;   doi:10.1038/sj.onc.1207353

PMID: 14676829 [PubMed - as supplied by publisher]

A phase II trial of green tea in the treatment of patients   with androgen independent metastatic prostate carcinoma.

Urol Oncol. 2003 Sep-Oct;21(5):409-10.

Jatoi A, Ellison N, Burch PA, Sloan JA, Dakhil SR, Novotny   P, Tan W, Fitch TR, Rowland KM, Young CY, Flynn PJ, Mayo Clinic and Mayo Foundation,   Rochester, MN. Cancer 2003;97:1442-1446.

Trump DL.

Recent laboratory and epidemiologic studies have suggested that   green tea has antitumor effects in patients with prostate carcinoma. This Phase   II trial explored green tea's antineoplastic effects in patients with androgen-independent   prostate carcinoma.This study, which was conducted by the North Central Cancer   Treatment Group, evaluated 42 patients who were asymptomatic and had manifested,   progressive prostate specific antigen (PSA) elevation with hormone therapy.   Continued use of luteinizing hormone-releasing hormone agonist was permitted;   however, patients were ineligible if they had received other treatments for   their disease in the preceding 4 weeks or if they had received a long-acting   antiandrogen therapy in the preceding 6 weeks. Patients were instructed to take   6 g of green tea per day orally in 6 divided doses. Each dose contained 100   calories and 46 mg of caffeine. Patients were monitored monthly for response   and toxicity.Tumor response, defined as a decline >/= 50% in the baseline   PSA value, occurred in a single patient, or 2% of the cohort (95% confidence   interval, 1-14%). This one response was not sustained beyond 2 months. At the   end of the first month, the median change in the PSA value from baseline for   the cohort increased by 43%. Green tea toxicity, usually Grade 1 or 2, occurred   in 69% of patients and included nausea, emesis, insomnia, fatigue, diarrhea,   abdominal pain, and confusion. However, six episodes of Grade 3 toxicity and   one episode of Grade 4 toxicity also occurred, with the latter manifesting as   severe confusion.Green tea carries limited antineoplastic activity, as defined   by a decline in PSA levels, among patients with androgen-independent prostate   carcinoma. Copyright 2003 American Cancer Society.

PMID: 14670556 [PubMed - in process]