1: Photochem Photobiol. 2005 Apr 1; [Epub ahead of print] Related Articles, Links Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of angiogenic factors and activation of CD8+ T cells in tumors. Mantena SK, Roy AM, Katiyar SK. University of Alabama At Birmingham. There has been a considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar ultraviolet (UV) radiation including photocarcinogenesis. We and others have shown that topical application of (-)epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice however, the chemopreventive mechanism of EGCG in in vivo tumor model is not clearly understood. In this study, UVB-induced skin tumors with and without treatment of EGCG ( approximately 1mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and anti-tumor immune response using immunostaining, western blotting and gelatinolytic zymography. We report that topical application of EGCG resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 in UV-induced tumors compared to non-EGCG treated tumors which play a crucial role in tumor growth and metastasis. In contrast, tissue inhibitor of MMP (TIMP1) which inhibits MMP activity was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UVB-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8+ T cells) were detected in EGCG treated tumors compared with non-EGCG treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity. PMID: 15938647 [PubMed - as supplied by publisher] 1: Cancer Lett. 2005 Jun 28;224(2):193-202. Epub 2004 Dec 10. Related Articles, Links Inhibition of tumour promotion in mouse skin by extracts of rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), unique South African herbal teas. Marnewick J, Joubert E, Joseph S, Swanevelder S, Swart P, Gelderblom W. PROMEC Unit, Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. The modulating effect of ethanol/acetone (E/A) soluble fractions, prepared from methanolic extracts of processed and unprocessed rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) as well as green (Camellia sinensis) teas was established in a two-stage mouse skin carcinogenesis assay. Topical application of the tea fractions prior to the tumour promoter, 12-Otetradecanoylphorbol-13-acetate (TPA), on ICR mouse skin initiated with 7,12dimethylbenz[a]anthracene (DMBA) suppressed skin tumorigenesis significantly (P<0.001) with the green tea E/A fraction exhibiting a 100% inhibition, unprocessed honeybush 90%, processed honeybush 84.2%, processed rooibos 75% and unprocessed rooibos 60%. The green tea fraction, with the highest flavanol/proanthocyanidin content, also exhibited the highest protective activity (99%) against hepatic microsomal lipid peroxidation, and completely inhibited skin tumour formation. Differences in the flavanol/proanthocyanidin and flavonol/flavone composition and/or non polyphenolic constituents are likely to be important determinants in the inhibition of tumour promotion by the herbal tea E/A fractions in mouse skin. PMID: 15914270 [PubMed - in process] 1: J Environ Pathol Toxicol Oncol. 2005;24(2):79-90. Related Articles, Links Inhibitory effect(s) of polymeric black tea polyphenols on the formation of B(a)P-derived DNA adducts in mouse skin. Krishnan R, Maru GB. Tobacco Carcinogenesis Group, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 208, India. The biological activities and chemopreventive properties of green tea polyphenols have been demonstrated, while similar information regarding newly formed major polymeric polyphenols in black tea are not available. Cancer chemoprevention may be achieved by the inhibition of any stage of carcinogenesis. In the present study, we investigated the anti-initiating effects of five polymeric black tea polyphenol (PBP) fractions, by determining their effects on the formation of [3H]B(a)P-derived DNA adducts as well as the activity of cytochrome P-450 isozymes CYP 1A1 and 1A2 in vitro employing rat liver microsomes. PBP 1-3 inhibited both the microsome catalyzed [3H]-B(a)P-derived DNA adduct formation as well as the activity of CYP 1A1 and 1A2 as assessed by the decreased formation of resorufin from the respective substrates. Further investigation revealed that topical pretreatment(s) of mice with PBP 1-5 (200 mug/day x 4) resulted in a significant decrease in the levels of single topical B(a)P (1 mg/mouse) - induced DNA adducts in epidermal DNA determined by employing 32P-post labeling analysis. Overall, our results suggest that black tea-derived PBPs have one of the chemopreventive properties shown by monomeric green tea polyphenols. PMID: 15831081 [PubMed - indexed for MEDLINE] 1: Carcinogenesis. 2005 Apr 7; [Epub ahead of print] Related Articles, Links Administration of green tea or caffeine enhances the disappearance of UVB-induced patches of mutant p53 positive epidermal cells in SKH-1 mice. Lu YP, Lou YR, Liao J, Xie JG, Peng QY, Yang CS, Conney AH. Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA. Irradiation of female SKH-1 hairless mice with UVB (30 mJ/cm(2)) twice a week for 10-20 weeks resulted in the formation of a large number of cellular patches (>8 adjacent cells/patch) that are recognized with an antibody (Pab240) that recognizes mutated but not wild-type p53 protein. These patches are not recognized by an antibody (Pab1620) to wild type p53 protein. The patches, which are considered putative early cellular markers of the beginning of tumor formation, started appearing after 4-6 weeks of UVB treatment, and multiple patches were observed after treatment for 10 weeks. The number and size of the patches increased progressively with continued UVB treatment. Discontinuation of UVB for 4 weeks resulted in an 80-90% decrease in the number of these patches. The number of remaining patches did not decrease further but remained relatively constant for at least 4-9 weeks. Oral administration of green tea (6 mg tea solids/ml) or caffeine (0.4 mg/ml) as the sole source of drinking fluid during twice a week irradiation with UVB for 20 weeks inhibited UVB-induced formation of mutant p53 positive patches by about 40%. Oral administration of green tea (6 mg tea solids/ml) as the sole source of drinking fluid or topical applications of caffeine (6.2 micromoles) once a day 5 days a week starting immediately after discontinuation of UVB treatment enhanced the rate and extent of disappearance of the mutant p53-positive patches. Topical applications of caffeine to the dorsal skin of mice pretreated with UVB for 20 weeks resulted in enhanced apoptosis selectively in focal basal cell hyperplastic areas of the epidermis (putative precancerous lesions), but not in areas of the epidermis that only had diffuse hyperplasia. Our studies indicate that the chemopreventive effect of caffeine or green tea may occur by a proapoptotic effect preferentially in early precancerous lesions. PMID: 15817611 [PubMed - as supplied by publisher] 1: FASEB J. 2005 May;19(7):807-9. Epub 2005 Feb 28. Related Articles, Links Green tea extract and (-)-epigallocatechin-3-gallate, the major tea catechin, exert oxidant but lack antioxidant activities. Elbling L, Weiss RM, Teufelhofer O, Uhl M, Knasmueller S, SchulteHermann R, Berger W, Micksche M. Institute of Cancer Research, Division of Applied and Experimental Oncology, Medical University of Vienna, Borschkegasse 8a, Vienna 1090, Austria. [email protected] Green tea is the most widely consumed beverage. It has attained high reputation as a health-promoting dietary component ascribed to the antioxidant activity of ()-epigallocatechin-3-gallate (EGCG), its main polyphenolic constituent. Evidence is increasing that tea constituents can be cell damaging and pro-oxidant themselves. These effects were suggested to be due to spontaneous H2O2 generation by polyphenols in solution. In the present study, we investigated the oxidant and antioxidant properties of green tea extracts (GTE) and of EGCG by means of the rodent macrophage-like RAW 264.7 and human promyelocytic leukemic HL60 cell lines. The results obtained show that both under cell-free conditions and in the presence of cells the oxidant activities of GTE and EGCG exceeded those of spontaneously generated H2O2 (FOX assay). Increase of intracellular oxidative stress was indicated by 2',7'-dichlorofluorescin probing, and the enhanced genotoxicity was demonstrated by the alkaline comet assay and by the micronucleus assay (cytokinesis block). Time- and dose-dependent induction of cell death was monitored by trypan blue exclusion, MTT assay, and Hoechst staining. Furthermore, in our systems in vitro, EGCG neither directly scavenges H2O2 nor mediates other antioxidant activities but rather increased H2O2-induced oxidative stress and DNA damage. In conclusion, our data suggest that detailed mechanistic studies on the effects of GTE and EGCG should be performed in vivo before excessive intake and/or topical application of green tea products can be recommended to healthy and/or diseased persons. PMID: 15738004 [PubMed - in process] 1: Oncogene. 2003 Dec 18;22(58):9254-64. Related Articles, Links Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice. Afaq F, Ahmad N, Mukhtar H. Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA. Studies from our laboratory have shown that epigallocatechin-3-gallate, the major polyphenol present in green tea, inhibits ultraviolet (UV)B-exposure-mediated phosphorylation of mitogen-activated protein kinases (MAPKs) (Toxicol. Appl. Pharmacol. 176: 110-117, 2001) and activation of nuclear factor kappa B (NFkappaB) (Oncogene 22: 1035-1044, 2003) pathways in normal human epidermal keratinocytes. This study was designed to investigate the relevance of these findings to the in vivo situations in SKH-1 hairless mouse model, which is regarded to have relevance to human situations. SKH-1 hairless mice were topically treated with GTP (5 mg/0.2 ml acetone/mouse) and were exposed to UVB 30 min later (180 mJ/cm2). These treatments were repeated every alternate day for 2 weeks, for a total of seven treatments. The animals were killed 24 h after the last UVB exposure. Topical application of GTP resulted in significant decrease in UVB-induced bifold-skin thickness, skin edema and infiltration of leukocytes. Employing Western blot analysis and immunohistochemical studies, we found that GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular-signal-regulated kinases (ERK1/2), (ii) c-Jun N-terminal kinases, and (iii) p38 protein expression. Since NF-kappaB plays a major role in inflammation and cell proliferation, we assessed the effect of GTP on UVBmediated modulations in the NF-kappaB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i) activation of NF-kappaB, (ii) activation of IKKalpha, and (iii) phosphorylation and degradation of IkappaBalpha. Our data suggest that GTP protects against the adverse effects of UV radiation via modulations in MAPK and NF-kappaB signaling pathways, and provides molecular basis for the photochemopreventive effect of GTP in an in vivo animal model system. PMID: 14681684 [PubMed - indexed for MEDLINE] 1: Eur J Cancer Prev. 2003 Oct;12(5):383-90. Related Articles, Links Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Ahn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, Bae SM, Lee IP. Department of Obstetrics and Gynaecology, College of Medicine, The Catholic University of Korea, Seoul, Korea. [email protected] We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 14512803 [PubMed - indexed for MEDLINE] 1: J Pharmacol Exp Ther. 2003 Oct;307(1):230-6. Epub 2003 Sep 3. Related Articles, Links Green tea polyphenol causes differential oxidative environments in tumor versus normal epithelial cells. Yamamoto T, Hsu S, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, Lockwood P, Ueta E, Osaki T, Schuster G. Kochi Medical School, Japan. Green tea polyphenols (GTPPs) are considered beneficial to human health, especially as chemopreventive agents. Recently, cytotoxic reactive oxygen species (ROS) were identified in tumor and certain normal cell cultures incubated with high concentrations of the most abundant GTPP, (-)-epigallocatechin-3gallate (EGCG). If EGCG also provokes the production of ROS in normal epithelial cells, it may preclude the topical use of EGCG at higher doses. The current study examined the oxidative status of normal epithelial, normal salivary gland, and oral carcinoma cells treated with EGCG, using ROS measurement and catalase and superoxide dismutase activity assays. The results demonstrated that high concentrations of EGCG induced oxidative stress only in tumor cells. In contrast, EGCG reduced ROS in normal cells to background levels. 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5bromodeoxyuridine incorporation data were also compared between the two oral carcinoma cell lines treated by EGCG, which suggest that a difference in the levels of endogenous catalase activity may play an important role in reducing oxidative stress provoked by EGCG in tumor cells. It is concluded that pathways activated by GTPPs or EGCG in normal epithelial versus tumor cells create different oxidative environments, favoring either normal cell survival or tumor cell destruction. This finding may lead to applications of naturally occurring polyphenols to enhance the effectiveness of chemo/radiation therapy to promote cancer cell death while protecting normal cells. PMID: 12954803 [PubMed - indexed for MEDLINE] 1: Recent Results Cancer Res. 2003;163:165-71; discussion 264-6. Related Articles, Links Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea. Linden KG, Carpenter PM, McLaren CE, Barr RJ, Hite P, Sun JD, Li KT, Viner JL, Meyskens FL. Department of Dermatology, University of California, Irvine, 101 The City Drive, Orange, CA 92868, USA. Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed. Publication Types: Review Review, Tutorial PMID: 12903852 [PubMed - indexed for MEDLINE] 1: Recent Results Cancer Res. 2003;163:151-64; discussion 264-6. Related Articles, Links Skin cancer chemoprevention: strategies to save our skin. Einspahr JG, Bowden GT, Alberts DS. Arizona Cancer Center, University of Arizona, P.O. Box 245024, Tucson, AZ 85724, USA. There are over 1 million cases of skin cancer diagnosed yearly in the United States. The majority of these are nonmelanoma (NMSCs) and are associated with chronic exposure to ultraviolet light (UV). Actinic keratosis (AK) has been identified as a precursor for SCC, but not for BCC. AKs are far more common than SCC, making them excellent targets for chemoprevention. Cancer chemoprevention can prevent or delay the occurrence of cancer in high-risk populations using dietary or chemical interventions. We have developed strategies that have rational mechanisms of action and demonstrate activity in preclinical models of skin cancer. Promising agents proceed to phase I-III trials in subjects at high risk of skin cancer. UV light induces molecular signaling pathways and results in specific genetic alterations (i.e., mutation of p53) that are likely critical to skin cancer development. UVB-induced changes serve as a basis for the development of novel agents. Targets include inhibition of polyamine or prostaglandin synthesis, specific retinoid receptors, and components of the Ras and MAP kinase signaling pathways. Agents under study include: epigallocatechin gallate (EGCG), a green tea catechin with antioxidant and sunscreen activity, as well as UVB signal transduction blocking activity; perillyl alcohol, a monoterpene derived from citrus peel that inhibits Ras farnesylation; difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase and polyamines; retinoids that target retinoid X receptors and AP-1 activity; and nonsteroidal anti-inflammatory agents that inhibit cylooxygenase and prostaglandin synthesis. We performed a series of Phase I-II trials in subjects with multiple AK. For example, a phase II randomized trial of topical DFMO reduced AK number, suppressed polyamines, and reduced p53 protein. Our goal is to develop agents for use in combination and/or incorporation into sunscreens to improve chemoprevention efficacy and reduce skin cancer incidence. Publication Types: Review Review, Tutorial PMID: 12903851 [PubMed - indexed for MEDLINE] 1: FASEB J. 2003 Oct;17(13):1913-5. Epub 2003 Aug 1. Related Articles, Links Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes. Chung JH, Han JH, Hwang EJ, Seo JY, Cho KH, Kim KH, Youn JI, Eun HC. Department of Dermatology, Seoul National University College of Medicine, and Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea. Beneficial effects attributed to green tea, such as its anticancer and antioxidant properties, may be mediated by (-)-epigallocatechin-3-gallate (EGCG). In this study, the effects of EGCG on cell proliferation and UV-induced apoptosis were investigated in normal epidermal keratinocytes. When topically applied to aged human skin, EGCG stimulated the proliferation of epidermal keratinocytes, which increased the epidermal thickness. In addition, this topical application also inhibited the UV-induced apoptosis of epidermal keratinocytes. EGCG was found to increase the phosphorylation of Bad protein at the Ser112 and Ser136. Moreover, EGCG-induced Erk phosphorylation was found to be critical for the phosphorylation of Ser112 in Bad protein, and the EGCG-induced activation of the Akt pathway was found to be involved in the phosphorylation of Ser136. Furthermore, EGCG increased Bcl-2 expression but decreased Bax expression, causing an increase in the Bcl-2-to-Bax ratio. In addition, we demonstrate the differential growth inhibitory effects of EGCG on cancer cells. In conclusion, this study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced apoptosis via two mechanisms: by phosphorylating Ser112 and Ser136 of Bad protein through Erk and Akt pathways, respectively, and by increasing the Bcl-2-to-Bax ratio. Moreover, these two proposed mechanisms of EGCG-induced cell proliferation may differ kinetically to promote keratinocyte survival. PMID: 12897059 [PubMed - indexed for MEDLINE] 1: Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42. Related Articles, Links Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Katiyar SK. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. [email protected] Because of a characteristic aroma and health benefits, green tea is consumed worldwide as a popular beverage. The epicatechin derivatives, commonly called polyphenols, present in green tea possess antioxidant, anti-inflammatory and anticarcinogenic properties. The major and most highly chemopreventive constituent in green tea responsible for the biochemical or pharmacological effects is (-)epigallocatechin-3-gallate (EGCG). Epidemiological, clinical and biological studies have implicated that solar ultraviolet (UV) light is a complete carcinogen and repeated exposure can lead to the development of various skin disorders including melanoma and nonmelanoma skin cancers. We and others have shown that topical treatment or oral consumption of green tea polyphenols (GTP) inhibit chemical carcinogen- or UV radiation-induced skin carcinogenesis in different laboratory animal models. Topical treatment of GTP and EGCG or oral consumption of GTP resulted in prevention of UVB-induced inflammatory responses, immunosuppression and oxidative stress, which are the biomarkers of several skin disease states. Topical application of GTP and EGCG prior to exposure of UVB protects against UVB-induced local as well as systemic immune suppression in laboratory animals, which was associated with the inhibition of UVB-induced infiltration of inflammatory leukocytes. Prevention of UVB-induced suppression of immune responses by EGCG was also associated with the reduction in immunosuppressive cytokine interleukin (IL)-10 production at UV irradiated skin and draining lymph nodes, whereas IL-12 production was significantly enhanced in draining lymph nodes. Antioxidant and antiinflammatory effects of green tea were also observed in human skin. Treatment of EGCG to human skin resulted in the inhibition of UVB-induced erythema, oxidative stress and infiltration of inflammatory leukocytes. We also showed that treatment of GTP to human skin prevents UVB-induced cyclobutane pyrimidine dimers formation, which are considered to be mediators of UVB-induced immune suppression and skin cancer induction. The in vitro and in vivo animal and human studies suggest that green tea polyphenols are photoprotective in nature, and can be used as pharmacological agents for the prevention of solar UVB light-induced skin disorders including photoaging, melanoma and nonmelanoma skin cancers after more clinical trials in humans. Publication Types: Review Review, Tutorial PMID: 12871030 [PubMed - indexed for MEDLINE] 1: Carcinogenesis. 2003 May;24(5):927-36. Related Articles, Links Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin. Vayalil PK, Elmets CA, Katiyar SK. Department of Dermatology, University of Alabama at Birmingham, 1670 University Blvd, Volker Hall 557, 35294, USA. The use of botanical supplements has received immense interest in recent years to protect human skin from adverse biological effects of solar ultraviolet (UV) radiation. The polyphenols from green tea are one of them and have been shown to prevent photocarcinogenesis in animal models but their mechanism of photoprotection is not well understood. To determine the mechanism of photoprotection in in vivo mouse model, topical treatment of polyphenols from green tea (GTP) or its most chemopreventive constituent (-)-epigallocatechin-3- gallate (EGCG) (1 mg/cm(2) skin area) in hydrophilic ointment USP before single (180 mJ/cm(2)) or multiple UVB exposures (180 mJ/cm(2), daily for 10 days) resulted in significant prevention of UVB-induced depletion of antioxidant enzymes such as glutathione peroxidase (78-100%, P < 0.005-0.001), catalase (51-92%, P < 0.001) and glutathione level (87-100%, P < 0.005). Treatment of EGCG or GTP also inhibited UVB-induced oxidative stress when measured in terms of lipid peroxidation (76-95%, P < 0.001), and protein oxidation (67-75%, P > 0.001). Further, to delineate the inhibition of UVB-induced oxidative stress with cell signaling pathways, treatment of EGCG to mouse skin resulted in marked inhibition of a single UVB irradiation-induced phosphorylation of ERK1/2 (16-95%), JNK (46-100%) and p38 (100%) proteins of MAPK family in a time-dependent manner. Identical photoprotective effects of EGCG or GTP were also observed against multiple UVB irradiation-induced phosphorylation of the proteins of MAPK family in vivo mouse skin. Photoprotective efficacy of GTP given in drinking water (d.w.) (0.2%, w/v) was also determined and compared with that of topical treatment of EGCG and GTP. Treatment of GTP in d.w. also significantly prevented single or multiple UVB irradiation-induced depletion of antioxidant enzymes (44-61%, P < 0.01-0.001), oxidative stress (3371%, P < 0.01) and phosphorylation of ERK1/2, JNK and p38 proteins of MAPK family but the photoprotective efficacy was comparatively less than that of topical treatments of EGCG and GTP. Lesser photoprotective efficacy of GTP in d.w. in comparison with topical application may be due to its less bioavailability in skin target cells. Together, for the first time a cream based formulation of green tea polyphenols was tested in this study to explore the possibility of its use for the humans, and the data obtained from this in vivo study further suggest that GTP could be useful in attenuation of solar UVB light-induced oxidative stressmediated and MAPK-caused skin disorders in humans. PMID: 12771038 [PubMed - indexed for MEDLINE] 1: Eur J Cancer Prev. 2002 Aug;11 Suppl 2:S28-36. Related Articles, Links Inhibitory effects of tea and caffeine on UV-induced carcinogenesis: relationship to enhanced apoptosis and decreased tissue fat. Conney AH, Lu YP, Lou YR, Huang MT. Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, NJ 08854, USA. Oral administration of green tea or caffeine to hairless SKH-1 mice for 2 weeks stimulated UV-induced increases in apoptotic sunburn cells in the epidermis, and a similar effect was observed when caffeine was applied topically immediately after UV. In mice pretreated with UV for 22 weeks (high-risk mice without tumors), topical applications of caffeine 5 days a week for 18 weeks with no further UV treatment inhibited carcinogenesis and stimulated apoptosis in the tumors. Oral administration of green or black tea to UV-pretreated high-risk mice for 23 weeks inhibited skin tumorigenesis, 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 to the decaffeinated teas restored their inhibitory effects. Administration of caffeine alone also inhibited carcinogenesis and decreased the size of the parametrial fat pads and the thickness of the dermal fat layer. Using data from individual mice and linear regression analysis, we found a highly significant positive correlation between the thickness of the dermal fat layer away from tumors and the number of tumors per mouse. PMID: 12570332 [PubMed - indexed for MEDLINE] 1: J Periodontal Res. 2002 Dec;37(6):433-8. Related Articles, Links Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study. Hirasawa M, Takada K, Makimura M, Otake S. Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba Japan. [email protected] The purpose of this study was to determine the usefulness of green tea catechin for the improvement of periodontal disease. The minimum inhibitory concentration (MIC) and bactericidal activity of green tea catechin against blackpigmented, Gram-negative anaerobic rods (BPR) were measured. Hydroxypropylcellulose strips containing green tea catechin as a slow release local delivery system were applied in pockets in patients once a week for 8 weeks. The clinical, enzymatic and microbiological effects of the catechin were determined. Green tea catechin showed a bactericidal effect against Porphyromonas gingivalis and Prevotella spp. in vitro with an MIC of 1.0 mg/ml. In the in vivo experiment, the pocket depth (PD) and the proportion of BPR were markedly decreased in the catechin group with mechanical treatment at week 8 compared with the baseline with significant difference. In contrast, PD and BPR were similar to the baseline and the value at the end of the experimental period in the placebo sites of scaled groups. The peptidase activities in the gingival fluid were maintained at lower levels during the experimental period in the test sites, while it reached 70% of that at baseline in the placebo sites. No morbidity was observed in the placebo and catechin groups without mechanical treatment. Green tea catechin showed a bactericidal effect against BPR and the combined use of mechanical treatment and the application of green tea catechin using a slow release local delivery system was effective in improving periodontal status. Publication Types: Clinical Trial Controlled Clinical Trial PMID: 12472837 [PubMed - indexed for MEDLINE] 1: Nutr Cancer. 2002;42(2):217-23. Related Articles, Links Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory skin edema and ornithine decarboxylase activity by theaflavin-3,3'-digallate in mouse. Liang YC, Tsai DC, Lin-Shiau SY, Chen CF, Ho CT, Lin JK. Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan. Among black tea polyphenols, theaflavins were generally considered to be the most effective in cancer chemoprevention. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), and the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema and ornithine decarboxylase (ODC) activity. Topical application of these polyphenols onto the mouse resulted in inhibition of TPA-induced ear edema and skin epidermal ODC activity. The inhibitory order was as follows: TF-3 > TF-2 approximately equal to EGCG > TF-1. Western and Northern blots indicated that TF-3 significantly reduced the protein and mRNA levels of ODC in TPA-treated mouse skin and NIH 3T3 cells, whereas EGCG showed less activity. EGCG and TF-3 were able to inhibit the ODC enzyme activity in vitro. Furthermore, TF-3 also significantly reduced the basal promoter activity of the ODC gene in NIH 3T3 cells that were transiently transfected with ODC reporter plasmid. These results suggested that TF-3 was a potential inhibitor of ODC activity and TPA-induced edema and might be effective in cancer chemoprevention.