Pharmaceutical Research

, Volume 27, Issue 6, pp 1066–1071

Effect of Dietary Polyphenon E and EGCG on Lung Tumorigenesis in A/J Mice

  • Qi Zhang
  • Huijing Fu
  • Jing Pan
  • Jun He
  • Seto Ryota
  • Yukihiko Hara
  • Yian Wang
  • Ronald A Lubet
  • Ming You
Research Paper



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.


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.


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.


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.


chemoprevention degradation EGCG lung tumorigenesis polyphenon E 

Supplementary material

11095_2010_56_MOESM1_ESM.doc (33 kb)
Supplementary Table 1Components of Poly E-EGCG and Poly E (DOC 33 kb)


  1. 1.
    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.CrossRefPubMedGoogle Scholar
  2. 2.
    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.Google Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    Hu C, Kitts DD. Evaluation of antioxidant activity of epigallocatechin gallate in biphasic model systems in vitro. Mol Cell Biochem. 2001;218:147–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol. 1999;58:911–5.CrossRefPubMedGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    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.PubMedGoogle Scholar
  12. 12.
    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.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    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.PubMedGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    Chen L, Lee MJ, Li H, Yang CS. Absorption, distribution, elimination of tea polyphenols in rats. Drug Metab Dispos. 1997;25:1045–50.PubMedGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    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.Google Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    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.CrossRefPubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedGoogle Scholar
  23. 23.
    Chen Z, Zhu QY, Tsang D, Huang Y. Degradation of green tea catechins in tea drinks. J Agric Food Chem. 2001;49:477–82.CrossRefPubMedGoogle Scholar
  24. 24.
    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.CrossRefPubMedGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Qi Zhang
    • 1
  • Huijing Fu
    • 2
  • Jing Pan
    • 1
  • Jun He
    • 1
  • Seto Ryota
    • 3
  • Yukihiko Hara
    • 3
  • Yian Wang
    • 1
  • Ronald A Lubet
    • 4
  • Ming You
    • 1
  1. 1.Department of Surgery and Alvin J Siteman Cancer CenterWashington University in St. LouisSt LouisUSA
  2. 2.Department of Energy, Environmental and Chemical EngineeringWashington University in St LouisSt. LouisUSA
  3. 3.Mitsui Norin Co., LtdShizuokaJapan
  4. 4.Chemoprevention Agent Development Research GroupNational Cancer InstituteBethesdaUSA

Personalised recommendations