This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, G. Articles by Yang, C. S. Search for Related Content PubMed PubMed Citation Articles by Lu, G. Articles by Yang, C. S. Related Collections Preclinical Intervention Preclinical Intervention: In Vivo (Animals): Drugs, Nutritional Interventions, Mechanisms

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

¹ Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology and ² Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey

Requests for reprints: Chung S. Yang, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854. Phone: 732-445-3400, ext. 244; Fax: 732-445-0687; E-mail: csyang{at}rci.rutgers.edu.

The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (–)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)–induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation. (Cancer Res 2006; 66(23): 11494-501)

This article has been cited by other articles:

				A. M. Bode and Z. Dong Epigallocatechin 3-Gallate and Green Tea Catechins: United They Work, Divided They Fail Cancer Prevention Research, June 1, 2009; 2(6): 514 - 517. [Full Text] [PDF]

				T. R. Church, K. E. Anderson, N. E. Caporaso, M. S. Geisser, C. T. Le, Y. Zhang, A. R. Benoit, S. G. Carmella, and S. S. Hecht A Prospectively Measured Serum Biomarker for a Tobacco-Specific Carcinogen and Lung Cancer in Smokers Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 260 - 266. [Abstract] [Full Text] [PDF]

				C.-M. Chen, H.-C. Chou, L.-F. Wang, and Y.-D. Lang Experimental Oligohydramnios Decreases Collagen in Hypoplastic Fetal Rat Lungs Experimental Biology and Medicine, November 1, 2008; 233(11): 1334 - 1340. [Abstract] [Full Text] [PDF]

				F. Kassie, I. Matise, M. Negia, D. Lahti, Y. Pan, R. Scherber, P. Upadhyaya, and S. S. Hecht Combinations of N-Acetyl-S-(N-2-Phenethylthiocarbamoyl)-L-Cysteine and myo-Inositol Inhibit Tobacco Carcinogen-Induced Lung Adenocarcinoma in Mice Cancer Prevention Research, September 1, 2008; 1(4): 285 - 297. [Abstract] [Full Text] [PDF]

				M. W. Anderson, C. Goodin, Y. Zhang, S. Kim, R. D. Estensen, T. S. Wiedmann, P. Sekar, C. R. Buncher, J. C. Khoury, J. R. Garbow, et al. Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in A/J strain mice Carcinogenesis, August 1, 2008; 29(8): 1594 - 1600. [Abstract] [Full Text] [PDF]

				D. J. Castro, Z. Yu, C. V. Lohr, C. B. Pereira, J. N. Giovanini, K. A. Fischer, G. A. Orner, R. H. Dashwood, and D. E. Williams Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine Carcinogenesis, August 1, 2008; 29(8): 1581 - 1586. [Abstract] [Full Text] [PDF]

				G. Lu, H. Xiao, H. You, Y. Lin, H. Jin, B. Snagaski, and C. S. Yang Synergistic Inhibition of Lung Tumorigenesis by a Combination of Green Tea Polyphenols and Atorvastatin Clin. Cancer Res., August 1, 2008; 14(15): 4981 - 4988. [Abstract] [Full Text] [PDF]

				E. A. Rogozin, K. W. Lee, N. J. Kang, H. Yu, M. Nomura, K.-I. Miyamoto, A. H. Conney, A. M. Bode, and Z. Dong Inhibitory effects of caffeine analogues on neoplastic transformation: structure-activity relationship Carcinogenesis, June 1, 2008; 29(6): 1228 - 1234. [Abstract] [Full Text] [PDF]