This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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, Y.-P. Articles by Conney, A. H. Search for Related Content PubMed PubMed Citation Articles by Lu, Y.-P. Articles by Conney, A. H.

Inhibitory Effects of Orally Administered Green Tea, Black Tea, and Caffeine on Skin Carcinogenesis in Mice Previously Treated with Ultraviolet B Light (High-Risk Mice)

Relationship to Decreased Tissue Fat¹

Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8020 [Y-P. L., Y-R. L., M-T. H., C. S. Y., A. H. C.]; University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901 [Y. L., W. J. S.]; and The Cancer Institute of New Jersey, New Brunswick, New Jersey 08901 [Y. L., W. J. S., M-T. H., C. S. Y., A. H. C.]

Treatment of SKH-1 hairless mice with ultraviolet B light (UVB; 30 mJ/cm²) twice a week for 22 weeks resulted in tumor-free animals with a high risk of developing malignant and nonmalignant skin tumors during the next several months in the absence of additional UVB treatment (high-risk mice). Oral administration of green tea or black tea (6 mg tea solids/ml) to UVB-pretreated high-risk SKH-1 mice for 23 weeks after stopping UVB treatment decreased the number of tumors/mouse, decreased the size of the parametrial fat pads, and decreased the thickness of the dermal fat layer away from tumors and directly under tumors. Administration of the decaffeinated teas had little or no effect on these parameters, and adding caffeine (equivalent to the amount in the regular teas) to the decaffeinated teas restored their inhibitory effects. Administration of caffeine alone also decreased the number of tumors/mouse, the size of the parametrial fat pads, and the thickness of the dermal fat layer away from tumors and under tumors. Using data from individual mice and linear regression and correlation analysis, we found a highly significant positive correlation between the thickness of the dermal fat layer away from tumors and the number of tumors/mouse (r = 0.34; P = 0.0001), but the correlation between average tumor size/mouse and the thickness of the dermal fat layer away from tumors was weak (r = 0.16; P = 0.034). The results suggested that p.o. administered tea or caffeine may have decreased tumor multiplicity in part by decreasing fat levels in the dermis. Additional analysis revealed that oral administration of caffeinated beverages (green tea, black tea, decaffeinated green tea plus caffeine, decaffeinated black tea plus caffeine, or caffeine alone) decreased the thickness of the dermal fat layer under large tumors to a much greater extent than under small tumors. This is the first demonstration of a close association between inhibition of carcinogenesis and the lowering of tissue fat levels by a chemopreventive agent.

This article has been cited by other articles:

				N. J. Kang, K. W. Lee, D. E. Lee, E. A. Rogozin, A. M. Bode, H. J. Lee, and Z. Dong Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase J. Biol. Chem., July 25, 2008; 283(30): 20664 - 20673. [Abstract] [Full Text] [PDF]

				Y.-P. Lu, B. Nolan, Y.-R. Lou, Q.-Y. Peng, G. C. Wagner, and A. H. Conney Voluntary exercise together with oral caffeine markedly stimulates UVB light-induced apoptosis and decreases tissue fat in SKH-1 mice PNAS, July 31, 2007; 104(31): 12936 - 12941. [Abstract] [Full Text] [PDF]

				M. Zhang, C. D. J. Holman, J.-p. Huang, and X. Xie Green tea and the prevention of breast cancer: a case-control study in Southeast China Carcinogenesis, May 1, 2007; 28(5): 1074 - 1078. [Abstract] [Full Text] [PDF]

				G. Lu, J. Liao, G. Yang, K. R. Reuhl, X. Hao, and C. S. Yang 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., December 1, 2006; 66(23): 11494 - 11501. [Abstract] [Full Text] [PDF]

				Y.-P. Lu, Y.-R. Lou, B. Nolan, Q.-Y. Peng, J.-G. Xie, G. C. Wagner, and A. H. Conney Stimulatory effect of voluntary exercise or fat removal (partial lipectomy) on apoptosis in the skin of UVB light-irradiated mice PNAS, October 31, 2006; 103(44): 16301 - 16306. [Abstract] [Full Text] [PDF]

				L. Michna, G. C. Wagner, Y.-R. Lou, J.-G. Xie, Q.-Y. Peng, Y. Lin, K. Carlson, W. J. Shih, A. H. Conney, and Y.-P. Lu Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice Carcinogenesis, October 1, 2006; 27(10): 2108 - 2115. [Abstract] [Full Text] [PDF]

				F. Spinella, L. Rosano, V. Di Castro, S. Decandia, A. Albini, M. R. Nicotra, P. G. Natali, and A. Bagnato Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma. Mol. Cancer Ther., June 1, 2006; 5(6): 1483 - 1492. [Abstract] [Full Text] [PDF]

				J. Janne, L. Alhonen, M. Pietila, T. A. Keinanen, A. Uimari, M. T. Hyvonen, E. Pirinen, and A. Jarvinen Genetic Manipulation of Polyamine Catabolism in Rodents J. Biochem., February 1, 2006; 139(2): 155 - 160. [Abstract] [Full Text] [PDF]

				J. Ju, J. Hong, J.-n. Zhou, Z. Pan, M. Bose, J. Liao, G.-y. Yang, Y. Y. Liu, Z. Hou, Y. Lin, et al. Inhibition of Intestinal Tumorigenesis in Apcmin/+ Mice by (-)-Epigallocatechin-3-Gallate, the Major Catechin in Green Tea Cancer Res., November 15, 2005; 65(22): 10623 - 10631. [Abstract] [Full Text] [PDF]

				W. J. Lee, J.-Y. Shim, and B. T. Zhu Mechanisms for the Inhibition of DNA Methyltransferases by Tea Catechins and Bioflavonoids Mol. Pharmacol., October 1, 2005; 68(4): 1018 - 1030. [Abstract] [Full Text] [PDF]

				M. Gu, S. Dhanalakshmi, R. P. Singh, and R. Agarwal Dietary Feeding of Silibinin Prevents Early Biomarkers of UVB Radiation-Induced Carcinogenesis in SKH-1 Hairless Mouse Epidermis Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1344 - 1349. [Abstract] [Full Text] [PDF]

				S. Dhanalakshmi, G.U. Mallikarjuna, R. P. Singh, and R. Agarwal Silibinin prevents ultraviolet radiation-caused skin damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and an up-regulation of p53-p21/Cip1 in epidermis Carcinogenesis, August 1, 2004; 25(8): 1459 - 1465. [Abstract] [Full Text] [PDF]

				P. A. Masso-Welch, D. Zangani, C. Ip, M. M. Vaughan, S. F. Shoemaker, S. O. McGee, and M. M. Ip Isomers of Conjugated Linoleic Acid Differ in Their Effects on Angiogenesis and Survival of Mouse Mammary Adipose Vasculature J. Nutr., February 1, 2004; 134(2): 299 - 307. [Abstract] [Full Text] [PDF]

				A. H. Conney Enzyme Induction and Dietary Chemicals as Approaches to Cancer Chemoprevention: The Seventh DeWitt S. Goodman Lecture Cancer Res., November 1, 2003; 63(21): 7005 - 7031. [Abstract] [Full Text] [PDF]

				H-H. S. Chow, Y. Cai, I. A. Hakim, J. A. Crowell, F. Shahi, C. A. Brooks, R. T. Dorr, Y. Hara, and D. S. Alberts Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose Administration of Epigallocatechin Gallate and Polyphenon E in Healthy Individuals Clin. Cancer Res., August 1, 2003; 9(9): 3312 - 3319. [Abstract] [Full Text] [PDF]

				A. Mittal, C. A. Elmets, and S. K. Katiyar Dietary feeding of proanthocyanidins from grape seeds prevents photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and lipid peroxidation Carcinogenesis, August 1, 2003; 24(8): 1379 - 1388. [Abstract] [Full Text] [PDF]

				F. Catterall, E. Copeland, M. N. Clifford, and C. Ioannides Effects of black tea theafulvins on aflatoxin B1 mutagenesis in the Ames test Mutagenesis, March 1, 2003; 18(2): 145 - 150. [Abstract] [Full Text] [PDF]

				Y.-P. Lu, Y.-R. Lou, J.-G. Xie, Q.-Y. Peng, J. Liao, C. S. Yang, M.-T. Huang, and A. H. Conney Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice PNAS, September 17, 2002; 99(19): 12455 - 12460. [Abstract] [Full Text] [PDF]

				M. Zhang, C. W. Binns, and A. H. Lee Tea Consumption and Ovarian Cancer Risk: A Case-Control Study in China Cancer Epidemiol. Biomarkers Prev., August 1, 2002; 11(8): 713 - 718. [Abstract] [Full Text] [PDF]