A New Concept of Tumor Promotion by Tumor Necrosis Factor-á, and Cancer Preventive Agents (-)-Epigallocatechin Gallate and Green Tea - A Review Hirota Fujiki, M.D., Masami Suganuma Ph.D., Sachiko Okabe, Elsaburo Sueoka, M.D., Kenji Suga, M.D., Kazue Imai Ph.D. and Kel Nakachi, Ph.D. Saitama Cancer Center Research Institute, Ina, Kitaadachi-gun, Saitama 362-0806, Japan **Present address: Saga Medical School, 5-1-1 Nabeshima, Saga 849-0937, Japan Address all correspondence to: Dr. Hirota Fajiki, Saitama Cancer Crater Research Institute, Ina, Kitaadachi-gun, Saitania362-0806, Japan. ABSTRACT The study of tumor promotion in rodent carcinogenesis using chemical tumor promoters has revealed various tumor promotion pathways, such as the 12-O-tetradecanoylphorbol-13-acetate (TPA) pathway mediated through activation of protein kinase C, and the okadaic acid pathway mediated through inhibition of protein phosphatases 1 and 2A (PP-l and PP-2A). We previously demonstrated that application of TPA and okadaicacid induced tumor necrosis factor-alpha (TNF-a) gene expression in mouse skin, but that tautomycin, which is an inhibitor of PP-I and PP-2A and not a tumor promoter on mouse skin, did not. Moreover, we found that TNF-stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene 1,000 times stronger than did TPA (Cancer Res. 53, 1982-1985, 1993). ‘This evidence demonstrates a link between the okadaic acid pathway and the endogenous tumor promotion pathway of TNF-alpha. Recently we presented the first evidence that tumor promotion in TNF-alpa-/- mice was significantly depressed compared with TNF-alpha+/+ mice. Thus, in human carcinogenesis,we think that TNF-alpha and other inflammatory cytokines in preneoplastic lesion stimulate tumor promotion and progression of initiated cells as well as premalignant cells. The first part of this paper reports on this TNF-alpha tamer promotion pathway. In the second part, we report a promising screening method for cancer preventive agents, based on evidence that pretreatment with agents such as tamoxifen, sulindac. Ice, 25-(OH)2 vitamin D3, quercetin, caffeic acidphenethyl ester, and (-)-epigallocatechin gallate (EGCG) commonly inhibited TNF-ce release from BALB/3T3 cells induced by okadaic acid. EGCG, the main constituent of Japanese green tea, and green tea itself are acknowledged cancer preventives in Japan, and this paper presents evidence of their effectiveness in both a high-risk group and the general population. Cancer Detection and Prevention 2000; 24(1):91-99. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.