ABSTRACT
Purpose
To compare the chemopreventive efficacy of Polyphenon E (Poly E), (−)-epigallocatechin-3-gallate (EGCG) and Polyphenon E without EGCG (Poly E-EGCG) on the development of benzo(a)pyrene (B(a)P)-induced lung tumors in A/J mice.
Methods
Female A/J mice were given a single intraperitoneal injection of B(a)P (100 mg/kg body weight). One week after B(a)P injection, animals received AIN-76A purified powder diet containing 0.975% (wt/wt) EGCG, 0.525% (wt/wt) Poly E-EGCG or 1.5% (wt/wt) Poly E for 24 weeks or control diet with no additives.
Results
Poly E treatment significantly decreased tumor multiplicity by 52% and tumor load by 64%, while EGCG and Poly E-EGCG did not significantly inhibit lung tumor multiplicity. EGCG was more stable in a complex mixture (Poly E) than as a pure compound.
Conclusion
EGCG was ineffective when administered by diet likely due to its instability. Thus, EGCG’s efficacy on mice lung tumorigenesis requires the presence of other tea catechins.
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REFERENCES
Chang PY, Mirsalis J, Riccio ES, Bakke JP, Lee PS, Shimon J, et al. Genotoxicity and toxicity of the potential cancer-preventive agent polyphenon E. Environ Mol Mutagen. 2003;41:43–54.
Fu HJ, He J, Mei F, Zhang Q, Hara Y, Ryota S, et al. Lung cancer inhibitory effect of epigallocatechin-3-gallate is dependent on its presence in a complex mixture (polyphenon E). Cancer Prev Res (Phila Pa). 2009;2:531–7.
Yan Y, Wang Y, Tan Q, Hara Y, Yun TK, Lubet RA, et al. Efficacy of polyphenon E, red ginseng, and rapamycin on benzo(a)pyrene-induced lung tumorigenesis in A/J mice. Neoplasia. 2006;8:52–8.
Yan Y, Cook J, McQuillan J, Zhang G, Hitzman CJ, Wang Y, et al. Chemopreventive effect of aerosolized polyphenon E on lung tumorigenesis in A/J mice. Neoplasia. 2007;9:401–5.
Anderson MW, Goodin C, Zhang Y, Kim S, Estensen RD, Wiedmann TS, et al. Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in A/J strain mice. Carcinogenesis. 2008;29:1594–600.
Lu G, Liao J, Yang G, Reuhl KR, Hao X, Yang CS. Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Res. 2006;66:11494–501.
Lu YP, Lou YR, Xie JG, Peng QY, Liao J, Yang CS, et al. Topical applications of caffeine or (−)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc Natl Acad Sci U S A. 2002;99:12455–60.
Hu C, Kitts DD. Evaluation of antioxidant activity of epigallocatechin gallate in biphasic model systems in vitro. Mol Cell Biochem. 2001;218:147–55.
Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol. 1999;58:911–5.
Hou Z, Lambert JD, Chin KV, Yang CS. Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention. Mutat Res. 2004;555:3–19.
Xu Y, Ho CT, Amin SG, Han C, Chung FL. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res. 1992;52:3875–9.
Mimoto J, Kiura K, Matsuo K, Yoshino T, Takata I, Ueoka H, et al. (−)-Epigallocatechin gallate can prevent cisplatin-induced lung tumorigenesis in A/J mice. Carcinogenesis. 2000;21:915–9.
Witschi H, Espiritu I, Ly M, Uyeminami D, Morin D, Raabe OG. Chemoprevention of tobacco smoke-induced lung tumors by inhalation of an epigallocatechin gallate (EGCG) aerosol: a pilot study. Inhal Toxicol. 2004;16:763–70.
Zhang Z, Liu Q, Lantry LE, Wang Y, Kelloff GJ, Anderson MW, et al. A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin. Cancer Res. 2000;60:901–7.
Wang Y, Zhang Z, Kastens E, Lubet RA, You M. Mice with alterations in both p53 and Ink4a/Arf display a striking increase in lung tumor multiplicity and progression: differential chemopreventive effect of budesonide in wild-type and mutant A/J mice. Cancer Res. 2003;63:4389–95.
Chen L, Lee MJ, Li H, Yang CS. Absorption, distribution, elimination of tea polyphenols in rats. Drug Metab Dispos. 1997;25:1045–50.
Sang S, Lee MJ, Hou Z, Ho CT, Yang CS. Stability of tea polyphenol (−)-epigallocatechin-3-gallate and formation of dimers and epimers under common experimental conditions. J Agric Food Chem. 2005;53:9478–84.
Raneva VG, Shimizu Y, Shimasaki H. Antioxidant activity in plasma and tissues distribution of (−)-epigallocatechin gallate after oral administration to rats. J Oleo Sci. 2005;54:289–98.
Liao J, Yang GY, Park ES, Meng X, Sun Y, Jia D, et al. Inhibition of lung carcinogenesis and effects on angiogenesis and apoptosis in A/J mice by oral administration of green tea. Nutr Cancer. 2004;48:44–53.
Yang CS, Yang GY, Landau JM, Kim S, Liao J. Tea and tea polyphenols inhibit cell hyperproliferation, lung tumorigenesis, and tumor progression. Exp Lung Res. 1998;24:629–39.
Cao J, Xu Y, Chen J, Klaunig JE. Chemopreventive effects of green and black tea on pulmonary and hepatic carcinogenesis. Fundam Appl Toxicol. 1996;29:244–50.
Lu H, Meng X, Yang CS. Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (−)-epigallocatechin gallate. Drug Metab Dispos. 2003;31:572–9.
Chen Z, Zhu QY, Tsang D, Huang Y. Degradation of green tea catechins in tea drinks. J Agric Food Chem. 2001;49:477–82.
Landis-Piwowar KR, Huo C, Chen D, Milacic V, Shi G, Chan TH, et al. A novel prodrug of the green tea polyphenol (−)-epigallocatechin-3-gallate as a potential anticancer agent. Cancer Res. 2007;67:4303–10.
Shimizu M, Deguchi A, Lim JT, Moriwaki H, Kopelovich L, Weinstein IB. (−)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin Cancer Res. 2005;11:2735–46.
ACKNOWLEDGEMENTS
This work was supported by NIH Grant R01CA139959 (Wang & You).
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Supplementary Table 1
Components of Poly E-EGCG and Poly E (DOC 33 kb)
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Zhang, Q., Fu, H., Pan, J. et al. Effect of Dietary Polyphenon E and EGCG on Lung Tumorigenesis in A/J Mice. Pharm Res 27, 1066–1071 (2010). https://doi.org/10.1007/s11095-010-0056-3
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DOI: https://doi.org/10.1007/s11095-010-0056-3