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Chemoprevention of Colon Carcinogenesis by Sulindac, a Nonsteroidal Anti-inflammatory Agent¹

Divisions of Nutritional Carcinogenesis [C. V. R., B. S., B. S. R.], Pathology and Toxicology [A. R.], and Epidemiology [E. Z.], American Health Foundation, Valhalla, New York 10595, and Chemoprevention Branch, Division of Cancer Control and Prevention, National Cancer Institute, Bethesda, Maryland 20892 [G. K., V. S.]

Epidemiological and laboratory animal model studies have suggested that nonsteroidal anti-inflammatory drugs reduce the risk of development of colon cancer. The present study was designed to investigate the chemopreventive action of 160 and 320 ppm (equivalent to 40 and 80% maximum tolerated doses) sulindac, a nonsteroidal anti-inflammatory drug, fed during initiation and postinitiation stages and 320 ppm sulindac fed during promotion/progression stages of azoxymethane-induced colon carcinogenesis in male F344 rats. Also investigated was the modulating effect of this agent on the colonic mucosal and tumor phospholipase A₂, phosphatidylinositol-specific phospholipase C, lipoxygenase, and cyclooxygenase activities. At 5 weeks of age, groups of male F344 rats were fed control diet or diets containing 160 and 320 ppm of sulindac. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. Animals intended for tumor promotion/progression study were administered 320 ppm of sulindac in diet starting at 14 weeks after a second azoxymethane treatment. All animals continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A₂, phosphatidylinositol-specific phospholipase C, prostaglandin E₂, cyclooxygenase, and lipoxygenase activities. The levels of sulindac and its metabolites in stomach, cecal, and fecal contents and in serum were analyzed. The results indicate that dietary sulindac at 160 and 320 ppm levels inhibited the incidence of invasive and nonivasive adenocarcinomas of the colon (P < 0.01–0.001) as well as their multiplicity (P < 0.01–0.0001) in a dose-dependent manner. Also, feeding sulindac during promotion/progression stages significantly suppressed the incidence (P < 0.0001) and multiplicity (P < 0.0001) of colonic adenocarcinomas. Dietary sulindac also suppressed the colon tumor volume by >52–62% compared to the control diet. Dietary sulindac significantly decreased the activities of phosphatidylinositol-specific phospholipase C (32–51%) and levels of prostaglandin E₂ (>40%) in the colonic mucosa and tumors, but it had no significant (P > 0.05) effect on phospholipase A₂ activity. The formation of cyclooxygenase metabolites, particularly prostaglandin E₂, prostaglandin F₂, prostaglandin D₂, 6-ketoprostaglandin F₁, and thromboxane B₂, and lipoxygenase metabolites such as 8(S)- and 12(S)-hydroxyeicosatetraenoic acids were significantly reduced in colonic mucosa and tumors of animals fed 320 ppm sulindac. Also, animals fed 320 ppm sulindac showed increased levels of microbial metabolites of sulindac in cecal and fecal contents and in serum as compared to those fed 160 ppm sulindac. Although the exact mechanism by which sulindac inhibits colon tumorigenesis remains to be elucidated, it is likely that its chemopreventive action, at least in part, may be related to the modulation of arachidonic acid metabolism.

¹ Supported by USPHS Grants CN85095-05 and CA17613 awarded by the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 11/21/94. Accepted 2/ 2/95.

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				J J Keller, G J A Offerhaus, M Polak, S N Goodman, M L Zahurak, L M Hylind, S R Hamilton, and F M Giardiello Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac Gut, December 1, 1999; 45(6): 822 - 828. [Abstract] [Full Text] [PDF]

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				A. P. Pentland, J. W. Schoggins, G. A. Scott, K. N. M. Khan, and R. Han Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition Carcinogenesis, October 1, 1999; 20(10): 1939 - 1944. [Abstract] [Full Text] [PDF]

				Y. Yamamoto, M.-J. Yin, K.-M. Lin, and R. B. Gaynor Sulindac Inhibits Activation of the NF-kappa B Pathway J. Biol. Chem., September 17, 1999; 274(38): 27307 - 27314. [Abstract] [Full Text] [PDF]

				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]

				S. R. Ritland, J. A. Leighton, R. E. Hirsch, J. D. Morrow, A. L. Weaver, and S. J. Gendler Evaluation of 5-Aminosalicylic Acid (5-ASA) for Cancer Chemoprevention: Lack of Efficacy against Nascent Adenomatous Polyps in the ApcMin Mouse Clin. Cancer Res., April 1, 1999; 5(4): 855 - 863. [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]

				B.L. Lokeshwar, H.L. Houston-Clark, M.G. Selzer, N.L. Block, and L.M. Golub Potential Application of a Chemically Modified Non-Antimicrobial Tetracycline (CMT-3) Against Metastatic Prostate Cancer Advances in Dental Research, November 1, 1998; 12(1): 97 - 102. [PDF]

				Z. Guan, S. Y. Buckman, A. P. Pentland, D. J. Templeton, and A. R. Morrison Induction of Cyclooxygenase-2 by the Activated MEKK1 right-arrow SEK1/MKK4 right-arrow p38 Mitogen-activated Protein Kinase Pathway J. Biol. Chem., May 22, 1998; 273(21): 12901 - 12908. [Abstract] [Full Text] [PDF]

				F. Zhang, K. Subbaramaiah, N. Altorki, and A. J. Dannenberg Dihydroxy Bile Acids Activate the Transcription of Cyclooxygenase-2 J. Biol. Chem., January 23, 1998; 273(4): 2424 - 2428. [Abstract] [Full Text] [PDF]

				L. E. Heasley, S. Thaler, M. Nicks, B. Price, K. Skorecki, and R. A. Nemenoff Induction of Cytosolic Phospholipase A2 by Oncogenic Ras in Human Non-small Cell Lung Cancer J. Biol. Chem., June 6, 1997; 272(23): 14501 - 14504. [Abstract] [Full Text] [PDF]

				B. J. Ledwith, C. J. Pauley, L. K. Wagner, C. L. Rokos, D. W. Alberts, and S. Manam Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells J. Biol. Chem., February 7, 1997; 272(6): 3707 - 3714. [Abstract] [Full Text] [PDF]

				P. C. Chulada and R. Langenbach Differential Inhibition of Murine Prostaglandin Synthase-1 and -2 by Nonsteroidal Anti-Inflammatory Drugs Using Exogenous and Endogenous Sources of Arachidonic Acid J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 606 - 613. [Abstract] [Full Text]

				R. J. Coffey, C. J. Hawkey, L. Damstrup, R. Graves-Deal, V. C. Daniel, P. J. Dempsey, R. Chinery, S. C. Kirkland, R. N. DuBois, T. L. Jetton, et al. Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells PNAS, January 21, 1997; 94(2): 657 - 662. [Abstract] [Full Text] [PDF]

				M. Murakami, H. Naraba, T. Tanioka, N. Semmyo, Y. Nakatani, F. Kojima, T. Ikeda, M. Fueki, A. Ueno, S. Oh-ishi, et al. Regulation of Prostaglandin E2 Biosynthesis by Inducible Membrane-associated Prostaglandin E2 Synthase That Acts in Concert with Cyclooxygenase-2 J. Biol. Chem., October 13, 2000; 275(42): 32783 - 32792. [Abstract] [Full Text] [PDF]