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 Michaluart, P. Articles by Dannenberg, A. J. Search for Related Content PubMed PubMed Citation Articles by Michaluart, P. Articles by Dannenberg, A. J.

Inhibitory Effects of Caffeic Acid Phenethyl Ester on the Activity and Expression of Cyclooxygenase-2 in Human Oral Epithelial Cells and in a Rat Model of Inflammation¹

Departments of Medicine and Surgery [K. S., A. J. D.], Joan and Sanford I. Weill Medical College of Cornell University and Anne Fisher Nutrition Center [K. S., J. R. M., A. J. D.] at Strang Cancer Prevention Center, New York, New York 10021; Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [P. M., J. R. M., P. G. S.]; Institute of Cancer Research, College of Physicians & Surgeons of Columbia University, New York, New York 10032 [A. M. C., D. G.]; Searle Discovery Research, Monsanto Co., St. Louis, Missouri 63167 [J. L. M., B. S. Z., C. K.]; and the Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka 565, Japan [T. T.]

We investigated the mechanisms by which caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, inhibited the stimulation of prostaglandin (PG) synthesis in cultured human oral epithelial cells and in an animal model of acute inflammation. Treatment of cells with CAPE (2.5 µg/ml) suppressed phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) and calcium ionophore (A23187)-mediated induction of PGE₂ synthesis. This relatively low concentration of CAPE did not affect amounts of cyclooxygenase (COX) enzymes. CAPE nonselectively inhibited the activities of baculovirus-expressed hCOX-1 and hCOX-2 enzymes. TPA- and A23187-stimulated release of arachidonic acid from membrane phospholipids was also suppressed by CAPE (4–8 µg/ml). Higher concentrations of CAPE (10–20 µg/ml) suppressed the induction of COX-2 mRNA and protein mediated by TPA. Transient transfections using human COX-2 promoter deletion constructs were performed; the effects of TPA and CAPE were localized to a 124-bp region of the COX-2 promoter. In the rat carrageenan air pouch model of inflammation, CAPE (10–100 mg/kg) caused dose-dependent suppression of PG synthesis. Amounts of COX-2 in the pouch were markedly suppressed by 100 mg/kg CAPE but were unaffected by indomethacin. These data are important for understanding the anticancer and anti-inflammatory properties of CAPE.

This article has been cited by other articles:

				H. Yilmaz, E Uz, O Gokalp, N Ozcelik, E Cicek, and M. Ozer Protective role of caffeic acid phenethyl ester and erdosteine on activities of purine-catabolizing enzymes and level of nitric oxide in red blood cells of isoniazid-administered rats Toxicology and Industrial Health, September 1, 2008; 24(8): 519 - 524. [Abstract] [PDF]

				O. Beltran-Ramirez, L. Aleman-Lazarini, M. Salcido-Neyoy, S. Hernandez-Garcia, S. Fattel-Fazenda, E. Arce-Popoca, J. Arellanes-Robledo, R. Garcia-Roman, P. Vazquez-Vazquez, A. Sierra-Santoyo, et al. Evidence that the Anticarcinogenic Effect of Caffeic Acid Phenethyl Ester in the Resistant Hepatocyte Model Involves Modifications of Cytochrome P450 Toxicol. Sci., July 1, 2008; 104(1): 100 - 106. [Abstract] [Full Text] [PDF]

				J. E. Jung, H. S. Kim, C. S. Lee, D.-H. Park, Y.-N. Kim, M.-J. Lee, J. W. Lee, J.-W. Park, M.-S. Kim, S. K. Ye, et al. Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells Carcinogenesis, August 1, 2007; 28(8): 1780 - 1787. [Abstract] [Full Text] [PDF]

				M. Guney, S. Nasir, B. Oral, N. Karahan, and T. Mungan Effect of Caffeic Acid Phenethyl Ester on the Regression of Endometrial Explants in an Experimental Rat Model Reproductive Sciences, April 1, 2007; 14(3): 270 - 279. [Abstract] [PDF]

				F. Oktem, H R. Yilmaz, F. Ozguner, S. Olgar, A. Ayata, E. Uzar, and E. Uz Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester Toxicology and Industrial Health, July 1, 2006; 22(6): 241 - 247. [Abstract] [PDF]

				F. Ozguner, A. Altinbas, M. Ozaydin, A. Dogan, H. Vural, A N. Kisioglu, G. Cesur, and N. G. Yildirim Mobile phone-induced myocardial oxidative stress: protection by a novel antioxidant agent caffeic acid phenethyl ester Toxicology and Industrial Health, August 1, 2005; 21(7-8): 223 - 230. [Abstract] [PDF]

				D.-B. Shieh, S.-R. Yang, X.-Y. Shi, Y.-N. Wu, and S.-N. Wu Properties of BKCa Channels in Oral Keratinocytes Journal of Dental Research, May 1, 2005; 84(5): 468 - 473. [Abstract] [Full Text] [PDF]

				T.-W. CHUNG, S.-K. MOON, Y.-C. CHANG, J.-H. KO, Y.-C. LEE, G. CHO, S.-H. KIM, J.-G. KIM, and C.-H. KIM Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism FASEB J, November 1, 2004; 18(14): 1670 - 1681. [Abstract] [Full Text] [PDF]

				N. Marquez, R. Sancho, A. Macho, M. A. Calzado, B. L. Fiebich, and E. Munoz Caffeic Acid Phenethyl Ester Inhibits T-Cell Activation by Targeting Both Nuclear Factor of Activated T-Cells and NF-{kappa}B Transcription Factors J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 993 - 1001. [Abstract] [Full Text] [PDF]

				L. LEVINE Does the release of arachidonic acid from cells play a role in cancer chemoprevention? FASEB J, May 1, 2003; 17(8): 800 - 802. [Abstract] [Full Text] [PDF]

				G. Scapagnini, R. Foresti, V. Calabrese, A. M. G. Stella, C. J. Green, and R. Motterlini Caffeic Acid Phenethyl Ester and Curcumin: A Novel Class of Heme Oxygenase-1 Inducers Mol. Pharmacol., March 1, 2002; 61(3): 554 - 561. [Abstract] [Full Text] [PDF]

				L. R. Fitzpatrick, J. Wang, and T. Le Caffeic Acid Phenethyl Ester, an Inhibitor of Nuclear Factor-kappa B, Attenuates Bacterial Peptidoglycan Polysaccharide-Induced Colitis in Rats J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 915 - 920. [Abstract] [Full Text] [PDF]

				K. Subbaramaiah, P. Bulic, Y. Lin, A. J. Dannenberg, and D. S. Pasco Development and Use of a Gene Promoter-Based Screen to Identify Novel Inhibitors of Cyclooxygenase-2 Transcription J Biomol Screen, April 1, 2001; 6(2): 101 - 110. [Abstract] [PDF]

				M. B. Sporn and N. Suh Chemoprevention of cancer Carcinogenesis, March 1, 2000; 21(3): 525 - 530. [Abstract] [Full Text] [PDF]

				M. J. Weyant, A. M. Carothers, M. E. Bertagnolli, and M. M. Bertagnolli Colon Cancer Chemopreventive Drugs Modulate Integrin-mediated Signaling Pathways Clin. Cancer Res., March 1, 2000; 6(3): 949 - 956. [Abstract] [Full Text]