Inhibition of oncogene expression by green tea and (-)-epigallocatechin gallate in mice.
The effects of tea drinking on the tobacco-specific nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse lung oncogene expression and the effect of topical application of the tea polyphenol component (-)-epigallocatechin-3-gallate (EGCG) on 12-O-tedradecanoylphorbol-13-acetate (TPA)-induced mouse skin oncogene expression were investigated. In the first experiment, mice were treated with NNK (1.3 mg/kg body wt ip) once a day for three days and were given 2% tea in drinking water during the whole experimental period. After four or eight weeks, the lung tissue of the mice treated with NNK displayed a significantly high level of expression in c-myc, c-raf, and c-H-ras oncogenes, and they were all inhibited by tea drinking with inhibitory rates of 50%, 20%, and 50%, respectively. In the second experiment, a single application of 10 nmol of TPA to mouse skin led to a marked increase in the transcripts' level of ornithine decarboxylase (ODC) gene, protein kinase C (PKC) gene, and c-myc oncogene at four hours after TPA administration. Topical application of EGCG (1 or 5 mumol) one hour before the application of TPA inhibited all TPA-induced gene expression in a dose-dependent fashion. These results confirm the anticarcinogenic effects of tea and suggest that a possible mechanism is the effect of tea on carcinogen-induced oncogene expression.
Hu
G
G
Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Beijing, People's Republic of China.
Han
C
C
Chen
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002273:Carcinogens; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D008168:Lung / Q000187:drug effects; D051379:Mice; D009602:Nitrosamines; D009857:Oncogenes / Q000187:drug effects* / Q000235:genetics; D009955:Ornithine Decarboxylase / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D020574:Proto-Oncogene Proteins c-sis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012867:Skin / Q000187:drug effects; D013662:Tea / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate
D000970:Antineoplastic Agents; D002273:Carcinogens; D009602:Nitrosamines; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D020574:Proto-Oncogene Proteins c-sis; D013662:Tea; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D002392:Catechin; C045651:epigallocatechin gallate; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D016283:Proto-Oncogene Proteins p21(ras); D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate