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 Reddy, B. S. Articles by Kelloff, G. Search for Related Content PubMed PubMed Citation Articles by Reddy, B. S. Articles by Kelloff, G.

Dose-related Inhibition of Colon Carcinogenesis by Dietary Piroxicam, a Nonsteroidal Antiinflammatory Drug, during Different Stages of Rat Colon Tumor Development¹

Division of Nutrition and Endocrinology [B. S. R.] and Experimental Pathology and Toxicology [H. M.], Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595; and Chemoprevention Branch Division of Cancer Control and Prevention, National Cancer Institute, Bethesda, Maryland 20892 [G. K.]

The effect of four dose levels of piroxicam administered during different stages of colon tumor development was studied in male F344 rats to obtain a data base on the efficacy of piroxicam as an inhibitor of colon carcinogenesis. Piroxicam was added at levels of 25, 50, 75, and 150 ppm to the NIH-07 open-formula diet and fed to male F344 rats starting 1, 13, and 23 wk after the carcinogen administration. At 7 wk of age, while the animals were consuming the control diet, all animals except the vehicle-treated controls were given s.c. injection of azoxymethane (CAS:25843-45-2; 29.6 mg/kg body weight, once) to induce intestinal tumors. Forty wk after AOM injection, all animals were necropsied, and tumor incidences were compared among the various dietary groups. Colon tumor incidence (percentage of animals with tumors) was inhibited in a dose-dependent manner in rats fed the diets containing 25, 50, 75, and 150 ppm piroxicam starting 1 and 13 wk after carcinogen treatment. The colon tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm of piroxicam starting at 1 wk after carcinogen treatment were 89, 61, 58, 50, and 39%, respectively. When the diets containing 0, 25, 50, 75, and 150 ppm were fed 13 wk after carcinogen treatment, the colon tumor incidences were 89, 69, 69, 44, and 33%, respectively. Colon tumor multiplicity (tumors/animal; tumors/tumor-bearing animal) was also significantly inhibited in animals fed the diets containing 25 to 150 ppm piroxicam starting 1 and 13 wk after carcinogen administration. The number of colon tumors/animal was inhibited by about 80 to 84% in animals fed the 150 ppm piroxicam diet. When the diets containing different levels of piroxicam were fed 23 wk after carcinogen treatment, the colon tumor incidence was significantly inhibited in animals fed the 75 and 150 ppm piroxicam diets. The colon tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm were 89, 78, 67, 64, and 64%, respectively. The colon tumor multiplicity (colon tumors/animal) was slightly but significantly inhbited in animals fed the diets containing 25 to 150 ppm piroxicam. The results of this study demonstrate that increasing levels of piroxicam in the diet, when fed 1 or 13 wk after carcinogen insult, inhibit colon tumor incidence in a dose-dependent manner.

¹ This investigation was supported by USPHS Contract NO1-CN-45191-01 from the National Cancer Institute. Animals were maintained under the guidelines set forth in the "Guide for the Care and Use of Laboratory Animal Resources" by the National Research Council.

² To whom requests for reprints should be addressed.

Received 4/30/87. Revised 7/17/87. Accepted 7/24/87.

This article has been cited by other articles:

				M. Ding, R. Feng, S. Y. Wang, L. Bowman, Y. Lu, Y. Qian, V. Castranova, B.-H. Jiang, and X. Shi Cyanidin-3-glucoside, a Natural Product Derived from Blackberry, Exhibits Chemopreventive and Chemotherapeutic Activity J. Biol. Chem., June 23, 2006; 281(25): 17359 - 17368. [Abstract] [Full Text] [PDF]

				B. A. Narayanan, N. K. Narayanan, B. Pittman, and B. S. Reddy Regression of Mouse Prostatic Intraepithelial Neoplasia by Nonsteroidal Anti-inflammatory Drugs in the Transgenic Adenocarcinoma Mouse Prostate Model Clin. Cancer Res., November 15, 2004; 10(22): 7727 - 7737. [Abstract] [Full Text] [PDF]

				D. L. Simmons, R. M. Botting, and T. Hla Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition Pharmacol. Rev., September 1, 2004; 56(3): 387 - 437. [Abstract] [Full Text] [PDF]

				A. P. Femia, P. Dolara, and G. Caderni Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis Carcinogenesis, February 1, 2004; 25(2): 277 - 281. [Abstract] [Full Text] [PDF]

				B. A. Narayanan, M. S. Condon, M. C. Bosland, N. K. Narayanan, and B. S. Reddy Suppression of N-Methyl-N-nitrosourea/Testosterone-induced Rat Prostate Cancer Growth by Celecoxib: Effects on Cyclooxygenase-2, Cell Cycle Regulation, and Apoptosis Mechanism(s) Clin. Cancer Res., August 1, 2003; 9(9): 3503 - 3513. [Abstract] [Full Text] [PDF]

				X. Chen, N. Li, S. Wang, J. Hong, M. Fang, J. Yousselfson, P. Yang, R. A. Newman, R. A. Lubet, and C. S. Yang Aberrant arachidonic acid metabolism in esophageal adenocarcinogenesis, and the effects of sulindac, nordihydroguaiaretic acid, and {alpha}-difluoromethylornithine on tumorigenesis in a rat surgical model Carcinogenesis, December 1, 2002; 23(12): 2095 - 2102. [Abstract] [Full Text] [PDF]

				P. S. Carlton, R. Gopalakrishnan, A. Gupta, B. W. Liston, S. Habib, M. A. Morse, and G. D. Stoner Piroxicam Is an Ineffective Inhibitor of N-Nitrosomethylbenzylamine-induced Tumorigenesis in the Rat Esophagus Cancer Res., August 1, 2002; 62(15): 4376 - 4382. [Abstract] [Full Text] [PDF]

				Z. Zhang, J. Li, L. E. Lantry, Y. Wang, R. W. Wiseman, R. A. Lubet, and M. You p53 Transgenic Mice Are Highly Susceptible to 1, 2-Dimethylhydrazine-induced Uterine Sarcomas Cancer Res., June 1, 2002; 62(11): 3024 - 3029. [Abstract] [Full Text] [PDF]

				M. J. Thun, S. J. Henley, and C. Patrono Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues J Natl Cancer Inst, February 20, 2002; 94(4): 252 - 266. [Abstract] [Full Text] [PDF]

				C. Rodriguez-Burford, M. N. Barnes, D. K. Oelschlager, R. B. Myers, L. I. Talley, E. E. Partridge, and W. E. Grizzle Effects of Nonsteroidal Anti-Inflammatory Agents (NSAIDs) on Ovarian Carcinoma Cell Lines: Preclinical Evaluation of NSAIDs as Chemopreventive Agents Clin. Cancer Res., January 1, 2002; 8(1): 202 - 209. [Abstract] [Full Text] [PDF]

				K. Yoshimatsu, N. K. Altorki, D. Golijanin, F. Zhang, P.-J. Jakobsson, A. J. Dannenberg, and K. Subbaramaiah Inducible Prostaglandin E Synthase Is Overexpressed in Non-Small Cell Lung Cancer Clin. Cancer Res., September 1, 2001; 7(9): 2669 - 2674. [Abstract] [Full Text] [PDF]

				M. Kojima, T. Morisaki, A. Uchiyama, F. Doi, R. Mibu, M. Katano, and M. Tanaka Association of Enhanced Cyclooxygenase-2 Expression With Possible Local Immunosuppression in Human Colorectal Carcinomas Ann. Surg. Oncol., June 1, 2001; 8(5): 458 - 465. [Abstract] [Full Text] [PDF]

				W. R. Bruce, A. Giacca, and A. Medline Possible Mechanisms Relating Diet and Risk of Colon Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2000; 9(12): 1271 - 1279. [Abstract] [Full Text]

				R. Calaluce, D. L. Earnest, D. Heddens, J. G. Einspahr, D. Roe, C. L. Bogert, J. R. Marshall, and D. S. Alberts Effects of Piroxicam on Prostaglandin E2 Levels in Rectal Mucosa of Adenomatous Polyp Patients: A Randomized Phase IIb Trial Cancer Epidemiol. Biomarkers Prev., December 1, 2000; 9(12): 1287 - 1292. [Abstract] [Full Text]

				Y Kishimoto, N Takata, T Jinnai, T Morisawa, G Shiota, H Kawasaki, and J Hasegawa Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane Gut, December 1, 2000; 47(6): 812 - 819. [Abstract] [Full Text] [PDF]

				C. Petersen, S. Petersen, L. Milas, F. F. Lang, and P. J. Tofilon Enhancement of Intrinsic Tumor Cell Radiosensitivity Induced by a Selective Cyclooxygenase-2 Inhibitor Clin. Cancer Res., June 1, 2000; 6(6): 2513 - 2520. [Abstract] [Full Text]

				B. S. Reddy Novel Approaches to the Prevention of Colon Cancer by Nutritional Manipulation and Chemoprevention Cancer Epidemiol. Biomarkers Prev., March 1, 2000; 9(3): 239 - 247. [Abstract] [Full Text]

				M. Tsutsumi, H. Kitada, K. Shiraiwa, M. Takahama, T. Tsujiuchi, H. Sakitani, Y. Sasaki, K. Murakawa, M. Yoshimoto, and Y. Konishi Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats Carcinogenesis, February 1, 2000; 21(2): 251 - 256. [Abstract] [Full Text] [PDF]

				P. F. Coogan, L. Rosenberg, J. R. Palmer, B. L. Strom, A. G. Zauber, P. D. Stolley, and S. Shapiro Nonsteroidal Anti-Inflammatory Drugs and Risk of Digestive Cancers at Sites Other Than the Large Bowel Cancer Epidemiol. Biomarkers Prev., January 1, 2000; 9(1): 119 - 123. [Abstract] [Full Text]

				D. Wolfle, S. Marotzki, D. Dartsch, W. Schafer, and H. Marquardt Induction of cyclooxygenase expression and enhancement of malignant cell transformation by 2,3,7,8-tetrachlorodibenzo- p-dioxin Carcinogenesis, January 1, 2000; 21(1): 15 - 21. [Abstract] [Full Text] [PDF]

				B. S. Reddy, Y. Hirose, R. Lubet, V. Steele, G. Kelloff, S. Paulson, K. Seibert, and C. V. Rao Chemoprevention of Colon Cancer by Specific Cyclooxygenase-2 Inhibitor, Celecoxib, Administered during Different Stages of Carcinogenesis Cancer Res., January 1, 2000; 60(2): 293 - 297. [Abstract] [Full Text]

				B. S. Reddy, T. Kawamori, R. Lubet, V. Steele, G. Kelloff, and C. V. Rao Chemopreventive effect of S-methylmethane thiosulfonate and sulindac administered together during the promotion/progression stages of colon carcinogenesis Carcinogenesis, August 1, 1999; 20(8): 1645 - 1648. [Abstract] [Full Text] [PDF]

				B. S. Reddy, T. Kawamori, R. A. Lubet, V. E. Steele, G. J. Kelloff, and C. V. Rao Chemopreventive Efficacy of Sulindac Sulfone against Colon Cancer Depends on Time of Administration during Carcinogenic Process Cancer Res., July 1, 1999; 59(14): 3387 - 3391. [Abstract] [Full Text] [PDF]

				J. D. Potter Colorectal Cancer: Molecules and Populations J Natl Cancer Inst, June 2, 1999; 91(11): 916 - 932. [Abstract] [Full Text] [PDF]

				H. Li, H. A.J. Schut, P. Conran, P. M. Kramer, R. A. Lubet, V. E. Steele, E. E. Hawk, G. J. Kelloff, and M. A. Pereira Prevention by aspirin and its combination with {alpha}-difluoromethylornithine of azoxymethane-induced tumors, aberrant crypt foci and prostaglandin E2 levels in rat colon Carcinogenesis, March 1, 1999; 20(3): 425 - 430. [Abstract] [Full Text] [PDF]

				T. Kawamori, R. Lubet, V. E. Steele, G. J. Kelloff, R. B. Kaskey, and C. V. Rao Chemopreventive Effect of Curcumin, a Naturally Occurring Anti-Inflammatory Agent, during the Promotion/Progression Stages of Colon Cancer Cancer Res., February 1, 1999; 59(3): 597 - 601. [Abstract] [Full Text] [PDF]

				H. Sawaoka, S. Kawano, S. Tsuji, M. Tsujii, E. S. Gunawan, Y. Takei, K. Nagano, and M. Hori Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice Am J Physiol Gastrointest Liver Physiol, June 1, 1998; 274(6): G1061 - G1067. [Abstract] [Full Text] [PDF]

				K. Narko, A. Ristimaki, M. MacPhee, E. Smith, C. C. Haudenschild, and T. Hla Tumorigenic Transformation of Immortalized ECV Endothelial Cells by Cyclooxygenase-1 Overexpression J. Biol. Chem., August 22, 1997; 272(34): 21455 - 21460. [Abstract] [Full Text] [PDF]

				E. Giovannucci, K. M. Egan, D. J. Hunter, M. J. Stampfer, G. A. Colditz, W. C. Willett, and F. E. Speizer Aspirin and the Risk of Colorectal Cancer in Women N. Engl. J. Med., September 7, 1995; 333(10): 609 - 614. [Abstract] [Full Text] [PDF]

				A. Saxena, M. Andley, and N. Gnanasekaran Comparison of piroxicam and acetylsalicylic acid for pain in head and neck cancers: a double-blind study Palliative Medicine, July 1, 1994; 8(3): 223 - 229. [Abstract] [PDF]