This Article 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 Katiyar, S. K. Articles by Mukhtar, H. Search for Related Content PubMed PubMed Citation Articles by Katiyar, S. K. Articles by Mukhtar, H.

Inhibition of 12-O-Tetradecanoylphorbol-13-acetate-caused Tumor Promotion in 7,12-Dimethylbenz[a]anthracene-initiated SENCAR Mouse Skin by a Polyphenolic Fraction Isolated from Green Tea¹

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

² To whom requests for reprints should be addressed, at the Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106.

Our laboratory has been studying cancer chemopreventive effects of polyphenolic fraction isolated from green tea (GTP). In prior studies we have shown that (a) GTP possesses antigenotoxic effects in various test systems; (b) topical application of GTP protects against UV radiation and chemical carcinogen-induced tumorigenesis in murine skin; and (c) feeding of GTP in drinking water p.o. to mice protects against carcinogen-induced forestomach and lung tumorigenesis. Recently, we showed that in a dose-dependent manner GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al., Cancer Res., 52: 3582–3588, 1992). In the present study, we assessed the effect of GTP on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of GTP (1–24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin tumor promotion in a dose-dependent manner. The animals pretreated with GTP showed substantially lower tumor body burden such as decrease in total number of tumors per group, number of tumors per animal, tumor volume per mouse, and average volume per tumor, as compared to the animals that did not receive GTP. Since TPA-induced epidermal cyclooxygenase and lipoxygenase activities and edema and hyperplasia are conventionally used markers of skin tumor promotion, we also assessed the effect of preapplication of GTP on these parameters. As quantitated by the formation of prostaglandin and hydroxy-eicosatetraenoic acid metabolites from, respectively, cyclooxygenase- and lipoxygenase-catalyzed metabolism of arachidonic acid, skin application of GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2 enzymes. Prior application of GTP to mouse skin also resulted in 30–46% inhibition of TPA-induced epidermal edema and hyperplasia. The results of the present study suggest that GTP possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-induced epidermal ornithine decarboxylase, cyclooxygenase and lipoxygenase activities, edema, and hyperplasia. Further studies are in progress to define which component present in GTP is responsible for its anti-skin tumor-promoting effects.

¹ This work is supported by USPHS Grants ES-1900 and P-30-AR-39750, American Institute for Cancer Research Grant 90A47, and by research funds from the Department of Veterans Affairs. R. A. is a recipient of a Dermatology Foundation Research Grant Award. Portions of this work were presented at the 83rd Annual Meeting of the the American Association of Cancer Research, San Diego, CA, 1992 (Proc. Am. Assoc. Cancer Res., 33: 168, 1992).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/25/92. Accepted 10/ 2/92.

This article has been cited by other articles:

				S. M. Meeran, M. Vaid, T. Punathil, and S. K. Katiyar Dietary grape seed proanthocyanidins inhibit 12-O-tetradecanoyl phorbol-13-acetate-caused skin tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated mouse skin, which is associated with the inhibition of inflammatory responses Carcinogenesis, March 1, 2009; 30(3): 520 - 528. [Abstract] [Full Text] [PDF]

				G. Deep and R. Agarwal Chemopreventive Efficacy of Silymarin in Skin and Prostate Cancer Integr Cancer Ther, June 1, 2007; 6(2): 130 - 145. [Abstract] [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]

				B. Frei and J. V. Higdon Antioxidant Activity of Tea Polyphenols In Vivo: Evidence from Animal Studies J. Nutr., October 1, 2003; 133(10): 3275S - 3284. [Abstract] [Full Text] [PDF]

				P. K. Vayalil, C. A. Elmets, and S. K. Katiyar Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin Carcinogenesis, May 1, 2003; 24(5): 927 - 936. [Abstract] [Full Text] [PDF]

				N. Khan, S. Sharma, and S. Sultana Nigella sativa (black cumin) ameliorates potassium bromate-induced early events of carcinogenesis: diminution of oxidative stress Human and Experimental Toxicology, April 1, 2003; 22(4): 193 - 203. [Abstract] [PDF]

				J. Hong, H. Lu, X. Meng, J.-H. Ryu, Y. Hara, and C. S. Yang Stability, Cellular Uptake, Biotransformation, and Efflux of Tea Polyphenol (-)-Epigallocatechin-3-Gallate in HT-29 Human Colon Adenocarcinoma Cells Cancer Res., December 15, 2002; 62(24): 7241 - 7246. [Abstract] [Full Text] [PDF]

				S. Gupta, K. Hastak, N. Ahmad, J. S. Lewin, and H. Mukhtar Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols PNAS, August 10, 2001; (2001) 171326098. [Abstract] [Full Text] [PDF]

				S. K. Katiyar, F. Afaq, A. Perez, and H. Mukhtar Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress Carcinogenesis, February 1, 2001; 22(2): 287 - 294. [Abstract] [Full Text] [PDF]

				M. Nomura, W.-y. Ma, N. Chen, A. M. Bode, and Z. Dong Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced NF-{kappa}B activation by tea polyphenols, (-)-epigallocatechin gallate and theaflavins Carcinogenesis, October 1, 2000; 21(10): 1885 - 1890. [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]

				H. Mukhtar and N. Ahmad Tea polyphenols: prevention of cancer and optimizing health Am. J. Clinical Nutrition, June 1, 2000; 71(6): 1698S - 1702. [Abstract] [Full Text] [PDF]

				J. Zhao, M. Lahiri-Chatterjee, Y. Sharma, and R. Agarwal Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin Carcinogenesis, April 1, 2000; 21(4): 811 - 816. [Abstract] [Full Text] [PDF]

				C. S. Yang, J. Y. Chung, G.-y. Yang, S. K. Chhabra, and M.-J. Lee Tea and Tea Polyphenols in Cancer Prevention J. Nutr., February 1, 2000; 130(2): 472 - 472. [Abstract] [Full Text]

				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]

				T. M. Haqqi, D. D. Anthony, S. Gupta, N. Ahmad, M.-S. Lee, G. K. Kumar, and H. Mukhtar Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea PNAS, April 13, 1999; 96(8): 4524 - 4529. [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]

				S. Gupta, K. Hastak, N. Ahmad, J. S. Lewin, and H. Mukhtar Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols PNAS, August 28, 2001; 98(18): 10350 - 10355. [Abstract] [Full Text] [PDF]