The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Hirota Fujiki - One of the best experts on this subject based on the ideXlab platform.
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Tumor Promoters - Microcystin-LR, Nodularin and TNF-α and Human Cancer Development
Anti-cancer Agents in Medicinal Chemistry, 2011Co-Authors: Hirota Fujiki, Masami SuganumaAbstract:: Microcystin-LR and nodularin, along with okadaic acid, are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A). The mechanisms of action of microcystin-LR and nodularin in the liver and that of okadaic acid, a potent Tumor Promoter on mouse skin, have attracted the attention of the scientists. This paper reviews several topics: new inhibitors of PP1 and PP2A with new chemical structures, structure-function relationships for both receptor binding and inhibition of protein phosphatases, the crystal structure of PP1 or PP2A-toxin complex, induction of gene expression and apoptosis. These subjects were studied by using in vitro and in vivo experimental systems. Two-stage carcinogenesis experiments with microcystin-LR and nodularin for the first time demonstrated that microcystin-LR is a new Tumor Promoter in rat liver initiated with diethylnitrosamine (DEN), and that nodularin is a potent Tumor Promoter associated with weak initiating activity in rat liver initiated with DEN. A working group of WHO (IARC) concluded that microcystin-LR is "possibly carcinogenic to humans" and that nodularin is "not classifiable as to carcinogenicity". Our studies revealed that chemical Tumor Promoters are inducers of TNF-α in the cells of target tissues and that TNF-α is an endogenous Tumor Promoter. This advance in carcinogenesis made it possible to look for the link between chemical Tumor Promoters and endogenous Tumor Promoters, such as TNF-α and IL-1. The carcinogenic features of TNF-α are described in this review, and the TNF-α inducing protein (Tipα) of Helicobacter pylori genome is presented as an example of a Tumor Promoter of human stomach cancer development.
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Expression of the Tumor necrosis factor α gene and early response genes by nodularin, a liver Tumor Promoter, in primary cultured rat hepatocytes
Journal of cancer research and clinical oncology, 1997Co-Authors: Eisaburo Sueoka, Tetsuya Ohta, Masami Suganuma, Atsumasa Komori, Naoko Sueoka, Sachiko Okabe, Tomoko Kozu, S. J. Kim, In Kyoung Lim, Hirota FujikiAbstract:Nodularin is a new liver carcinogen possessing a potent Tumor-promoting activity in rat liver, mediated through inhibition of protein phosphatases 1 and 2A, and a weak initiating activity. Since we previously reported evidence that nodularin up-regulated expression of the Tumor necrosis factor α gene (TNFα) and early-response genes in rat liver after its i.p. administration, and since TNFα had Tumor-promoting activity in vitro, it is possible that TNFα itself is involved in liver Tumor promotion. We investigated whether hepatocytes themselves induce expression of theTNFα gene and early-response genes in primary cultured rat hepatocytes treated with nodularin. Like nodularin, microcystin-LR, which is another liver Tumor Promoter belonging to the okadaic acid class, strongly inducedTNFα gene expression in rat hepatocytes, as well as TNFα release from those cells into the medium. On the other hand, 12-O-tetradecanoylphorbol-13-acetate, which has been reported to induce no Tumor promotion in rat liver, induced no apparent expression of theTNFα gene in primary cultured rat hepatocytes. As for the expression of early-response genes, 1 μM nodularin or microcystin-LR induced expression of the c-jun, jun B,jun D, c-fos, fos B andfra-1 genes in the hepatocytes, and the expression of these genes was prolonged up to 24 h, suggesting mRNA stabilization induced by inhibition of protein phosphatases 1 and 2A. This paper presents new evidence that theTNFα gene and early-response genes were expressed in hepatocytes treated with a liver Tumor Promoter.
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expression of the Tumor necrosis factor alpha gene and early response genes by nodularin a liver Tumor Promoter in primary cultured rat hepatocytes
Journal of Cancer Research and Clinical Oncology, 1997Co-Authors: Eisaburo Sueoka, Tetsuya Ohta, Masami Suganuma, Atsumasa Komori, Seong Jin Kim, Naoko Sueoka, Sachiko Okabe, Tomoko Kozu, In Kyoung Lim, Hirota FujikiAbstract:Nodularin is a new liver carcinogen possessing a potent Tumor-promoting activity in rat liver, mediated through inhibition of protein phosphatases 1 and 2A, and a weak initiating activity. Since we previously reported evidence that nodularin up-regulated expression of the Tumor necrosis factor α gene (TNFα) and early-response genes in rat liver after its i.p. administration, and since TNFα had Tumor-promoting activity in vitro, it is possible that TNFα itself is involved in liver Tumor promotion. We investigated whether hepatocytes themselves induce expression of theTNFα gene and early-response genes in primary cultured rat hepatocytes treated with nodularin. Like nodularin, microcystin-LR, which is another liver Tumor Promoter belonging to the okadaic acid class, strongly inducedTNFα gene expression in rat hepatocytes, as well as TNFα release from those cells into the medium. On the other hand, 12-O-tetradecanoylphorbol-13-acetate, which has been reported to induce no Tumor promotion in rat liver, induced no apparent expression of theTNFα gene in primary cultured rat hepatocytes. As for the expression of early-response genes, 1 μM nodularin or microcystin-LR induced expression of the c-jun, jun B,jun D, c-fos, fos B andfra-1 genes in the hepatocytes, and the expression of these genes was prolonged up to 24 h, suggesting mRNA stabilization induced by inhibition of protein phosphatases 1 and 2A. This paper presents new evidence that theTNFα gene and early-response genes were expressed in hepatocytes treated with a liver Tumor Promoter.
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a new process of cancer prevention mediated through inhibition of Tumor necrosis factor α expression
Cancer Research, 1996Co-Authors: Masami Suganuma, Eisaburo Sueoka, Naoyuki Iida, Atsumasa Komori, Seong Jin Kim, Sachiko Okabe, Hirota FujikiAbstract:Abstract Mechanisms of cancer prevention were studied using structurally different cancer-preventive agents, sarcophytol A, canventol, (-)-epigallocatechin gallate, and tamoxifen, based on our evidence that Tumor necrosis factor α (TNF-α) acts as an endogenous Tumor Promoter relevant to human carcinogenesis. Pretreatment with the four preventive agents commonly inhibited TNF -α mRNA expression and TNF-α release in BALB/3T3 cells induced by a Tumor Promoter, okadaic acid, whereas the expression of early response genes (c- jun , jun B, c- fos , and fos B) was enhanced. These results strongly suggest that inhibition of TNF -α mRNA expression and its release is a new process of cancer prevention.
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Nodularin, a Potent Inhibitor of Protein Phosphatases 1 and 2A, Is a New Environmental Carcinogen in Male F344 Rat Liver
Cancer research, 1994Co-Authors: Tetsuya Ohta, Masami Suganuma, Wayne W. Carmichael, Eisaburo Sueoka, Naoyuki Iida, Atsumasa Komori, Rie Nishiwaki, Masae Tatematsu, Seong Jin Kim, Hirota FujikiAbstract:Abstract Nodularin and microcystin-LR are cyanobacterial toxins and environmental hazards. Nodularin inhibits protein phosphatases 1 and 2A with the same potency as does microcystin-LR, which has recently been identified as a potent Tumor Promoter in rat liver. Our results suggested that nodularin is also a new Tumor Promoter in rat liver. A two-stage carcinogenesis experiment in rat liver initiated with diethylnitrosamine and without partial hepatectomy revealed that nodularin stimulated glutathione S -transferase placental form-positive foci in rat liver more effectively than did microcystin-LR, and that nodularin alone induced glutathione S -transferase placental form-positive foci as well as did diethylnitrosamine alone. Thus, nodularin itself is a new liver carcinogen, and microcystin-LR is a Tumor Promoter rather than a carcinogen. Nodularin induced hyperphosphorylation of cytokeratin peptides 8 and 18 in primary cultured rat hepatocytes 20% more effectively than did microcystin-LR, suggesting that nodularin penetrates more easily into the hepatocytes than does microcystin-LR. Nodularin up-regulated induction of c- jun, jun -B, jun -D, c- fos, fos -B, and fra -1 mRNA transcripts in rat liver after i.p. administration, and the accumulation of the mRNA transcripts was sustained for over 9 h after treatment. The environmental hazards of cyanobacterial toxins are discussed in relation to human primary liver cancer in Qidong county in the People9s Republic of China. Our results support this hypothesis and indicate the need for prevention measures against cyanobacterial toxins.
Masami Suganuma - One of the best experts on this subject based on the ideXlab platform.
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Tumor Promoters - Microcystin-LR, Nodularin and TNF-α and Human Cancer Development
Anti-cancer Agents in Medicinal Chemistry, 2011Co-Authors: Hirota Fujiki, Masami SuganumaAbstract:: Microcystin-LR and nodularin, along with okadaic acid, are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A). The mechanisms of action of microcystin-LR and nodularin in the liver and that of okadaic acid, a potent Tumor Promoter on mouse skin, have attracted the attention of the scientists. This paper reviews several topics: new inhibitors of PP1 and PP2A with new chemical structures, structure-function relationships for both receptor binding and inhibition of protein phosphatases, the crystal structure of PP1 or PP2A-toxin complex, induction of gene expression and apoptosis. These subjects were studied by using in vitro and in vivo experimental systems. Two-stage carcinogenesis experiments with microcystin-LR and nodularin for the first time demonstrated that microcystin-LR is a new Tumor Promoter in rat liver initiated with diethylnitrosamine (DEN), and that nodularin is a potent Tumor Promoter associated with weak initiating activity in rat liver initiated with DEN. A working group of WHO (IARC) concluded that microcystin-LR is "possibly carcinogenic to humans" and that nodularin is "not classifiable as to carcinogenicity". Our studies revealed that chemical Tumor Promoters are inducers of TNF-α in the cells of target tissues and that TNF-α is an endogenous Tumor Promoter. This advance in carcinogenesis made it possible to look for the link between chemical Tumor Promoters and endogenous Tumor Promoters, such as TNF-α and IL-1. The carcinogenic features of TNF-α are described in this review, and the TNF-α inducing protein (Tipα) of Helicobacter pylori genome is presented as an example of a Tumor Promoter of human stomach cancer development.
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Expression of the Tumor necrosis factor α gene and early response genes by nodularin, a liver Tumor Promoter, in primary cultured rat hepatocytes
Journal of cancer research and clinical oncology, 1997Co-Authors: Eisaburo Sueoka, Tetsuya Ohta, Masami Suganuma, Atsumasa Komori, Naoko Sueoka, Sachiko Okabe, Tomoko Kozu, S. J. Kim, In Kyoung Lim, Hirota FujikiAbstract:Nodularin is a new liver carcinogen possessing a potent Tumor-promoting activity in rat liver, mediated through inhibition of protein phosphatases 1 and 2A, and a weak initiating activity. Since we previously reported evidence that nodularin up-regulated expression of the Tumor necrosis factor α gene (TNFα) and early-response genes in rat liver after its i.p. administration, and since TNFα had Tumor-promoting activity in vitro, it is possible that TNFα itself is involved in liver Tumor promotion. We investigated whether hepatocytes themselves induce expression of theTNFα gene and early-response genes in primary cultured rat hepatocytes treated with nodularin. Like nodularin, microcystin-LR, which is another liver Tumor Promoter belonging to the okadaic acid class, strongly inducedTNFα gene expression in rat hepatocytes, as well as TNFα release from those cells into the medium. On the other hand, 12-O-tetradecanoylphorbol-13-acetate, which has been reported to induce no Tumor promotion in rat liver, induced no apparent expression of theTNFα gene in primary cultured rat hepatocytes. As for the expression of early-response genes, 1 μM nodularin or microcystin-LR induced expression of the c-jun, jun B,jun D, c-fos, fos B andfra-1 genes in the hepatocytes, and the expression of these genes was prolonged up to 24 h, suggesting mRNA stabilization induced by inhibition of protein phosphatases 1 and 2A. This paper presents new evidence that theTNFα gene and early-response genes were expressed in hepatocytes treated with a liver Tumor Promoter.
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expression of the Tumor necrosis factor alpha gene and early response genes by nodularin a liver Tumor Promoter in primary cultured rat hepatocytes
Journal of Cancer Research and Clinical Oncology, 1997Co-Authors: Eisaburo Sueoka, Tetsuya Ohta, Masami Suganuma, Atsumasa Komori, Seong Jin Kim, Naoko Sueoka, Sachiko Okabe, Tomoko Kozu, In Kyoung Lim, Hirota FujikiAbstract:Nodularin is a new liver carcinogen possessing a potent Tumor-promoting activity in rat liver, mediated through inhibition of protein phosphatases 1 and 2A, and a weak initiating activity. Since we previously reported evidence that nodularin up-regulated expression of the Tumor necrosis factor α gene (TNFα) and early-response genes in rat liver after its i.p. administration, and since TNFα had Tumor-promoting activity in vitro, it is possible that TNFα itself is involved in liver Tumor promotion. We investigated whether hepatocytes themselves induce expression of theTNFα gene and early-response genes in primary cultured rat hepatocytes treated with nodularin. Like nodularin, microcystin-LR, which is another liver Tumor Promoter belonging to the okadaic acid class, strongly inducedTNFα gene expression in rat hepatocytes, as well as TNFα release from those cells into the medium. On the other hand, 12-O-tetradecanoylphorbol-13-acetate, which has been reported to induce no Tumor promotion in rat liver, induced no apparent expression of theTNFα gene in primary cultured rat hepatocytes. As for the expression of early-response genes, 1 μM nodularin or microcystin-LR induced expression of the c-jun, jun B,jun D, c-fos, fos B andfra-1 genes in the hepatocytes, and the expression of these genes was prolonged up to 24 h, suggesting mRNA stabilization induced by inhibition of protein phosphatases 1 and 2A. This paper presents new evidence that theTNFα gene and early-response genes were expressed in hepatocytes treated with a liver Tumor Promoter.
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a new process of cancer prevention mediated through inhibition of Tumor necrosis factor α expression
Cancer Research, 1996Co-Authors: Masami Suganuma, Eisaburo Sueoka, Naoyuki Iida, Atsumasa Komori, Seong Jin Kim, Sachiko Okabe, Hirota FujikiAbstract:Abstract Mechanisms of cancer prevention were studied using structurally different cancer-preventive agents, sarcophytol A, canventol, (-)-epigallocatechin gallate, and tamoxifen, based on our evidence that Tumor necrosis factor α (TNF-α) acts as an endogenous Tumor Promoter relevant to human carcinogenesis. Pretreatment with the four preventive agents commonly inhibited TNF -α mRNA expression and TNF-α release in BALB/3T3 cells induced by a Tumor Promoter, okadaic acid, whereas the expression of early response genes (c- jun , jun B, c- fos , and fos B) was enhanced. These results strongly suggest that inhibition of TNF -α mRNA expression and its release is a new process of cancer prevention.
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Specific protein interacting with a Tumor Promoter, debromoaplysiatoxin, in bovine serum is α1-acid glycoprotein
Journal of cancer research and clinical oncology, 1995Co-Authors: Hisao Ueyama, Ichiro Sasaki, Kyoichi Shimomura, Masami SuganumaAbstract:Aplysiatoxin and debromoaplysiatoxin, a debrominated form of aplysiatoxin, have both been shown to be potent Tumor Promoters in a two-stage carcinogenesis experiment on mouse skin. However, debromoaplysiatoxin did not behave like aplysiatoxin in most of the biological assay systems using cultured cells. The discrepancy was supposed to be due to a factor in the bovine serum used for culture, a similar factor not being present in sera of eight other animal species examined. The factor was purified to homogeneity from bovine serum by ammonium sulfate fractionation and chromatographies on DEAE-cellulose, Sephadex G-150, hydroxyapatite, and a reversed-phase HPLC column. The factor was a 40-kDa protein, and partial amino-acid sequencing of its tryptic peptides indicated that the factor is α1-acid glycoprotein. Both the purified factor and the commercially available bovine α1-acid glycoprotein abolished in vitro the activation of protein kinase C by debromoaplysiatoxin but not that by aplysiatoxin. Debromoaplysiatoxin induced differentiation of HL-60 cells into macrophages at a comparable concentration to aplysiatoxin, when serum-free medium was used. These results suggest that α1-acid glycoprotein, which interacts specifically with debromoaplysiatoxin, contained in bovine serum must have masked the in vitro properties of the Tumor Promoter in the biological assay systems.
Hoyoku Nishino - One of the best experts on this subject based on the ideXlab platform.
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isolation structural elucidation and inhibitory effects of terpenoid and lipid constituents from sunflower pollen on epstein barr virus early antigen induced by Tumor Promoter tpa
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Motohiko Ukiya, Harukuni Tokuda, Toshihiro Akihisa, Kazuo Koike, Junko Takayasu, Hiroki Okuda, Yumiko Kimura, Tamotsu Nikaido, Hoyoku NishinoAbstract:Eight fatty acid esters of triterpene alcohols (1−8), four free triterpene alcohols (9, 12, 17, and 18), four diterpene acids (19−22), two tocopherol-related compounds (23 and 24), four estolides (25−28), three syn-alkane-4,6-diols (29−31), one 1,3-dioxoalkanoic acid (32), and one aliphatic ketone (33), along with the mixture of free fatty acids, were isolated from the diethyl ether extract of the pollen grains of sunflower (Helianthus annuus). Among these compounds, 14 (2−8, 12, 23, 25−28, and 33) were new naturally occurring compounds, and their structures were determined on the basis of spectroscopic methods. Twenty-four terpenoids and lipids (1−4, 6−9, 12, and 19−33) and six free triterpene triols (10, 11, and 13−16), derived from their fatty acid esters (2, 3, and 5−8) by alkaline hydrolysis, were evaluated with respect to their inhibitory effects on the induction of Epstein−Barr virus early antigen (EBV-EA) induced by the Tumor Promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells, whi...
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constituents of compositae plants iii anti Tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers
Cancer Letters, 2002Co-Authors: Motohiko Ukiya, Harukuni Tokuda, Toshihiro Akihisa, Hiroyuki Suzuki, Teruo Mukainaka, Eiichiro Ichiishi, Ken Yasukawa, Yoshimasa Kasahara, Hoyoku NishinoAbstract:Fifteen pentacyclic triterpene diols and triols, consisting of: six taraxastanes, faradiol (1), heliantriol B0 (2), heliantriol C (3), 22alpha-methoxyfaradiol (4), arnidiol (5), and faradiol alpha-epoxide (6); five oleananes, maniladiol (7), erythrodiol (8), longispinogenin (9), coflodiol (10), and heliantriol A(1) (11); two ursanes, brein (12) and uvaol (13); and two lupanes, calenduladiol (14) and heliantriol B2 (15), isolated from the non-saponifiable lipid fraction of the edible flower extract of chrysanthemum (Chrysanthemum morifolium) were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the Tumor Promoter, 12-O-tetradecanoylphorbol-13-acetate, in Raji cells as a primary screening test for anti-Tumor-Promoters. All of the compounds tested showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of glycyrrhetic acid, a known natural anti-Tumor-Promoter. Evaluation of the cytotoxic activity of six compounds, 1-3 and 5-7, against human cancer cell lines revealed that compound 5 possesses a wide range of cytotoxicity, with GI50 values (concentration that yields 50% growth) of mostly less than 6 microM.
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trichothecinols a b and c potent anti Tumor promoting sesquiterpenoids from the fungus trichothecium roseum
Tetrahedron Letters, 1996Co-Authors: Akira Iida, Kazuhide Konishi, Hiroki Kubo, Kiyoshi Tomioka, Harukuni Tokuda, Hoyoku NishinoAbstract:Abstract Three new trichothecenes, trichothecinols A (1), B (2) and C (3) were isolated from the fungus Trichothecium roseum and unambiguously characterized on the basis of spectroscopic and chemical evidence. These exhibited potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the Tumor Promoter 12- O -tetradecanoylphorbol-13-acetate (TPA).
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new teleocidin related metabolites 7 geranylindolactam v and blastmycetin f from streptoverticillium blastmyceticum
Journal of Natural Products, 1994Co-Authors: Kazuhiro Irie, Hoyoku Nishino, Koichi Koshimizu, Shin'ichiro Kajiyama, Motoo Arai, Shigenori Okuno, Masaru Kondo, Hideo Hayashi, Akio IwashimaAbstract:: Two new teleocidin-related metabolites, (-)-7-geranylindolactam-V [2] and blastmycetin F [3], were isolated from fermentation broths of the actinomycete Streptoverticillium blastmyceticum NA34-17, and their structures were determined by spectroscopic methods. Compound 2 bound strongly to phorbol ester receptors in a mouse epidermal particulate fraction, suggesting that it is a potent in vivo Tumor Promoter comparable to teleocidins A-1 [4] and B-4 [5].
H Mukhtar - One of the best experts on this subject based on the ideXlab platform.
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inhibition of phorbol ester Tumor Promoter 12 o tetradecanoylphorbol 13 acetate caused inflammatory responses in sencar mouse skin by black tea polyphenols
Carcinogenesis, 1997Co-Authors: Santosh K Katiyar, H MukhtarAbstract:Over the past 10 years many studies from several laboratories defined anticarcinogenic and anti-inflammatory effects of tea, a widely consumed beverage by the human population. Much of such work has been conducted with green tea or its polyphenolic constituents. Regarding black tea, studies have shown that its water extract affords protection against Tumor promotion caused by chemical carcinogens or ultraviolet B radiation in murine skin carcinogenesis models. Several studies have shown that topical application of chemical Tumor Promoters to murine skin results in the induction of epidermal edema, hyperplasia and ornithine decarboxylase (ODC) and cyclo-oxygenase activities, and interleukin-1 alpha (IL-1alpha) and ODC mRNA expression. In this study, we assessed whether topical application of polyphenols isolated from black tea leaves (hereafter referred to as BTP) mainly consisting of theaflavine gallates and (-)-epigallocatechin-3-gallate, inhibits phorbol ester Tumor Promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of these markers of inflammatory responses in murine skin. Topical application of BTP (6 mg in 0.2 ml acetone/animal) 30 min prior to TPA application on to the mouse skin resulted in significant inhibition against TPA-caused induction of epidermal edema (40%, P < 0.01), hyperplasia (57%, P < 0.005), leukocytes infiltration (50%), and induction of epidermal ODC (57%) and pro-inflammatory cytokine IL-1alpha mRNA expression (69%). Pre-application of BTP to that of TPA also resulted in significant inhibition of TPA-caused induction of epidermal ODC (23-73%, P < 0.005-0.0001), and cyclo-oxygenase, in terms of prostaglandins metabolites formation (38-65%, P < 0.01-0.0005), enzyme activities. Our data indicate that the inhibition of TPA-caused changes in these markers of inflammatory responses in murine skin by BTP may be one of the possible mechanisms of chemopreventive effects associated with black tea against Tumorigenesis. The results of this study suggest that black tea, specifically polyphenols present therein, may be useful against cutaneous inflammatory responses in human population.
Santosh K Katiyar - One of the best experts on this subject based on the ideXlab platform.
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inhibition of phorbol ester Tumor Promoter 12 o tetradecanoylphorbol 13 acetate caused inflammatory responses in sencar mouse skin by black tea polyphenols
Carcinogenesis, 1997Co-Authors: Santosh K Katiyar, H MukhtarAbstract:Over the past 10 years many studies from several laboratories defined anticarcinogenic and anti-inflammatory effects of tea, a widely consumed beverage by the human population. Much of such work has been conducted with green tea or its polyphenolic constituents. Regarding black tea, studies have shown that its water extract affords protection against Tumor promotion caused by chemical carcinogens or ultraviolet B radiation in murine skin carcinogenesis models. Several studies have shown that topical application of chemical Tumor Promoters to murine skin results in the induction of epidermal edema, hyperplasia and ornithine decarboxylase (ODC) and cyclo-oxygenase activities, and interleukin-1 alpha (IL-1alpha) and ODC mRNA expression. In this study, we assessed whether topical application of polyphenols isolated from black tea leaves (hereafter referred to as BTP) mainly consisting of theaflavine gallates and (-)-epigallocatechin-3-gallate, inhibits phorbol ester Tumor Promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of these markers of inflammatory responses in murine skin. Topical application of BTP (6 mg in 0.2 ml acetone/animal) 30 min prior to TPA application on to the mouse skin resulted in significant inhibition against TPA-caused induction of epidermal edema (40%, P < 0.01), hyperplasia (57%, P < 0.005), leukocytes infiltration (50%), and induction of epidermal ODC (57%) and pro-inflammatory cytokine IL-1alpha mRNA expression (69%). Pre-application of BTP to that of TPA also resulted in significant inhibition of TPA-caused induction of epidermal ODC (23-73%, P < 0.005-0.0001), and cyclo-oxygenase, in terms of prostaglandins metabolites formation (38-65%, P < 0.01-0.0005), enzyme activities. Our data indicate that the inhibition of TPA-caused changes in these markers of inflammatory responses in murine skin by BTP may be one of the possible mechanisms of chemopreventive effects associated with black tea against Tumorigenesis. The results of this study suggest that black tea, specifically polyphenols present therein, may be useful against cutaneous inflammatory responses in human population.
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inhibition of skin Tumor Promoter caused induction of epidermal ornithine decarboxylase in sencar mice by polyphenolic fraction isolated from green tea and its individual epicatechin derivatives
Cancer Research, 1992Co-Authors: Rajesh Agarwal, Santosh K Katiyar, Syed I A Zaidi, Hasan MukhtarAbstract:Green tea, next to water, is the most popular and commonly consumed beverage in the world, especially in eastern countries. In prior studies we have shown that the polyphenolic fraction isolated from green tea (GTP) exerts antigenotoxic effects in various mutagenicity test systems (Mutat. Res., 223: 273–285, 1989) and that its topical application or oral feeding in drinking water protects against polycyclic aromatic hydrocarbon-induced skin Tumor initiation and complete carcinogenesis in SENCAR and BALB/c mice [Cancer Lett., 42: 7–12, 1988; Carcinogenesis (Lond.), 10: 411–415, 1989] and UV B radiation-induced photocarcinogenesis in SKH-1 hairless mice [Carcinogenesis (Lond.), 12: 1527–1530, 1991]. In the present study we assessed the effect of skin application of GTP to SENCAR mice on 12- O -tetradecanoylphorbol-13-acetate (TPA) and other skin Tumor Promoter-caused induction of epidermal ornithine decarboxylase (ODC) activity. Topical application of GTP to mouse skin inhibited TPA-induced epidermal ODC activity in a dose-dependent manner. The inhibitory effect of GTP was also dependent on the time of its application relative to TPA treatment. Maximum inhibitory effect was observed when GTP was applied 30 min prior to topical application of TPA. GTP application to animals also inhibited the induction of epidermal ODC activity caused by several structurally different mouse skin Tumor Promoters. In order to identify which of the specific epicatechin derivatives present in GTP is responsible for these inhibitory effects, they were isolated from GTP and evaluated for their inhibitory effects against TPA-caused induction of epidermal ODC activity. Among these, (−)epigallocatechin-3-gallate (EGCG), which was the major constituent present in GTP by weight, exerted the maximum inhibition. EGCG also showed greater inhibitory effects against TPA-caused induction of epidermal ODC activity when compared with several other naturally occurring polyphenols. The results of this study suggest that GTP, specifically its epicatechin derivative EGCG, could provide anti-Tumor-promoting effects against a wide spectrum of skin Tumor Promoters.
