This Article 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 Agarwal, R. Articles by Mukhtar, H. Search for Related Content PubMed PubMed Citation Articles by Agarwal, R. Articles by Mukhtar, H.

Inhibition of Skin Tumor Promoter-caused Induction of Epidermal Ornithine Decarboxylase in SENCAR Mice by Polyphenolic Fraction Isolated from Green Tea and Its Individual Epicatechin Derivatives¹

Department of Dermatology, Skin Diseases Research Center, University Hospitals of Cleveland, Case Western Reserve University, and Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106

Green tea, next to water, is the most popular and commonly consumed beverage in the world, especially in eastern countries. In prior studies we have shown that the polyphenolic fraction isolated from green tea (GTP) exerts antigenotoxic effects in various mutagenicity test systems (Mutat. Res., 223: 273–285, 1989) and that its topical application or oral feeding in drinking water protects against polycyclic aromatic hydrocarbon-induced skin tumor initiation and complete carcinogenesis in SENCAR and BALB/c mice [Cancer Lett., 42: 7–12, 1988; Carcinogenesis (Lond.), 10: 411–415, 1989] and UV B radiation-induced photocarcinogenesis in SKH-1 hairless mice [Carcinogenesis (Lond.), 12: 1527–1530, 1991]. In the present study we assessed the effect of skin application of GTP to SENCAR mice on 12-O-tetradecanoylphorbol-13-acetate (TPA) and other skin tumor promoter-caused induction of epidermal ornithine decarboxylase (ODC) activity. Topical application of GTP to mouse skin inhibited TPA-induced epidermal ODC activity in a dose-dependent manner. The inhibitory effect of GTP was also dependent on the time of its application relative to TPA treatment. Maximum inhibitory effect was observed when GTP was applied 30 min prior to topical application of TPA. GTP application to animals also inhibited the induction of epidermal ODC activity caused by several structurally different mouse skin tumor promoters. In order to identify which of the specific epicatechin derivatives present in GTP is responsible for these inhibitory effects, they were isolated from GTP and evaluated for their inhibitory effects against TPA-caused induction of epidermal ODC activity. Among these, (–)epigallocatechin-3-gallate (EGCG), which was the major constituent present in GTP by weight, exerted the maximum inhibition. EGCG also showed greater inhibitory effects against TPA-caused induction of epidermal ODC activity when compared with several other naturally occurring polyphenols. The results of this study suggest that GTP, specifically its epicatechin derivative EGCG, could provide anti-tumor-promoting effects against a wide spectrum of skin tumor promoters.

¹ Supported by USPHS Grants ES-1900 and P-30-AR-39750, American Institute for Cancer Research Grant 90A47, and research funds from the Department of Veterans Affairs.

² R. A. is a recipient of a Dermatology Foundation Research Grant Award.

³ To whom requests for reprints should be addressed, at the Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106.

Received 1/ 9/92. Accepted 4/24/92.

This article has been cited by other articles:

				S. Balasubramanian, M. T. Sturniolo, G. R. Dubyak, and R. L. Eckert Human epidermal keratinocytes undergo (-)-epigallocatechin-3-gallate-dependent differentiation but not apoptosis Carcinogenesis, June 1, 2005; 26(6): 1100 - 1108. [Abstract] [Full Text] [PDF]

				M. Kaur, C. Agarwal, R. P. Singh, X. Guan, C. Dwivedi, and R. Agarwal Skin cancer chemopreventive agent, {alpha}-santalol, induces apoptotic death of human epidermoid carcinoma A431 cells via caspase activation together with dissipation of mitochondrial membrane potential and cytochrome c release Carcinogenesis, February 1, 2005; 26(2): 369 - 380. [Abstract] [Full Text] [PDF]

				B. Paul, C. S. Hayes, A. Kim, M. Athar, and S. K. Gilmour Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice Carcinogenesis, January 1, 2005; 26(1): 119 - 124. [Abstract] [Full Text] [PDF]

				J. K. Kundu, H.-K. Na, K.-S. Chun, Y.-K. Kim, S. J. Lee, S. S. Lee, O.-S. Lee, Y.-C. Sim, and Y.-J. Surh Inhibition of Phorbol Ester-Induced COX-2 Expression by Epigallocatechin Gallate in Mouse Skin and Cultured Human Mammary Epithelial Cells J. Nutr., November 1, 2003; 133(11): 3805S - 3810. [Abstract] [Full Text] [PDF]

				C. Dwivedi, X. Guan, W. L. Harmsen, A. L. Voss, D. E. Goetz-Parten, E. M. Koopman, K. M. Johnson, H. B. Valluri, and D. P. Matthees Chemopreventive Effects of {alpha}-Santalol on Skin Tumor Development in CD-1 and SENCAR Mice Cancer Epidemiol. Biomarkers Prev., February 1, 2003; 12(2): 151 - 156. [Abstract] [Full Text] [PDF]

				N. Ahmad, A. C. Gilliam, S. K. Katiyar, T. G. O'Brien, and H. Mukhtar A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis Am. J. Pathol., September 1, 2001; 159(3): 885 - 892. [Abstract] [Full Text] [PDF]

				K. M.W. Pisters, R. A. Newman, B. Coldman, D. M. Shin, F. R. Khuri, W. K. Hong, B. S. Glisson, and J. S. Lee Phase I Trial of Oral Green Tea Extract in Adult Patients With Solid Tumors J. Clin. Oncol., March 15, 2001; 19(6): 1830 - 1838. [Abstract] [Full Text] [PDF]

				K. Sai, J. Kanno, R. Hasegawa, J. E. Trosko, and T. Inoue Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenol Carcinogenesis, September 1, 2000; 21(9): 1671 - 1676. [Abstract] [Full Text] [PDF]

				S. K. Katiyar, N. Ahmad, and H. Mukhtar Green Tea and Skin Arch Dermatol, August 1, 2000; 136(8): 989 - 994. [Abstract] [Full Text] [PDF]

				C. Agarwal, Y. Sharma, J. Zhao, and R. Agarwal A Polyphenolic Fraction from Grape Seeds Causes Irreversible Growth Inhibition of Breast Carcinoma MDA-MB468 Cells by Inhibiting Mitogen-activated Protein Kinases Activation and Inducing G1 Arrest and Differentiation Clin. Cancer Res., July 1, 2000; 6(7): 2921 - 2930. [Abstract] [Full Text]

				J. Zhao and R. Agarwal Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention Carcinogenesis, November 1, 1999; 20(11): 2101 - 2108. [Abstract] [Full Text] [PDF]

				J. Zhao, J. Wang, Y. Chen, and R. Agarwal Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation–promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent Carcinogenesis, September 1, 1999; 20(9): 1737 - 1745. [Abstract] [Full Text] [PDF]

				D. A. August, J. Landau, D. Caputo, J. Hong, M.-J. Lee, and C. S. Yang Ingestion of Green Tea Rapidly Decreases Prostaglandin E2 Levels in Rectal Mucosa in Humans Cancer Epidemiol. Biomarkers Prev., August 1, 1999; 8(8): 709 - 713. [Abstract] [Full Text]

				S. Gupta, N. Ahmad, R. R. Mohan, M. M. Husain, and H. Mukhtar Prostate Cancer Chemoprevention by Green Tea: In Vitro and in Vivo Inhibition of Testosterone-mediated Induction of Ornithine Decarboxylase Cancer Res., May 1, 1999; 59(9): 2115 - 2120. [Abstract] [Full Text] [PDF]

				M. Lahiri-Chatterjee, S. K. Katiyar, R. R. Mohan, and R. Agarwal A Flavonoid Antioxidant, Silymarin, Affords Exceptionally High Protection against Tumor Promotion in the SENCAR Mouse Skin Tumorigenesis Model Cancer Res., February 1, 1999; 59(3): 622 - 632. [Abstract] [Full Text] [PDF]

				R. R. Mohan, A. Challa, S. Gupta, D. G. Bostwick, N. Ahmad, R. Agarwal, S. R. Marengo, S. B. Amini, F. Paras, G. T. MacLennan, et al. Overexpression of Ornithine Decarboxylase in Prostate Cancer and Prostatic Fluid in Humans Clin. Cancer Res., January 1, 1999; 5(1): 143 - 147. [Abstract] [Full Text] [PDF]

				C. A. Elmets, M. Athar, K. A. Tubesing, D. Rothaupt, H. Xu, and H. Mukhtar Susceptibility to the biological effects of polyaromatic hydrocarbons is influenced by genes of the major histocompatibility complex PNAS, December 8, 1998; 95(25): 14915 - 14919. [Abstract] [Full Text] [PDF]