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 Rao, C. V. Articles by Reddy, B. S. Search for Related Content PubMed PubMed Citation Articles by Rao, C. V. Articles by Reddy, B. S.

Chemoprevention of Colon Carcinogenesis by Phenylethyl-3-methylcaffeate¹

Divisions of Nutritional Carcinogenesis [C. V. R., B. S., B. S. R.], Chemical Carcinogenesis [D. D., S. A.], and Pathology and Toxicology [A. R.], American Health Foundation, Valhalla, New York 10595

Previous studies from this laboratory have established that caffeic acid esters present in propolis, a natural resin produced by honey bees, are potent inhibitors of human colon adenocarcinoma cell growth, carcinogen-induced biochemical changes, and preneoplastic lesions in the rat colon. The present study was designed to investigate the chemopreventive action of dietary phenylethyl-3-methylcaffeate (PEMC) on azoxymethane-induced colon carcinogenesis and to examine the modulating effect of PEMC on phosphatidylinositol-specific phospholipase C (PI-PLC), phospholipase A₂, lipoxygenase (LOX), and cyclooxygenase activities in the colonic mucosa and tumor tissues in male F344 rats. At 5 weeks of age, groups of rats were fed the control (modified AIN-76A) diet, or a diet containing 750 ppm of PEMC. At 7 weeks of age, all animals except those in the vehicle (normal saline)-treated groups were given 2 weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. All groups were maintained on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Both colonic mucosa and tumors were analyzed for PI-PLC, phospholipase A₂, cyclooxygenase, and LOX activities. The results indicate that dietary administration of PEMC significantly inhibited the incidence and multiplicity of invasive, noninvasive, and total (invasive plus noninvasive) adenocarcinomas of the colon (P < 0.05–0.004). Dietary PEMC also suppressed the colon tumor volume by 43% compared to the control diet. Animals fed the PEMC diet showed significantly decreased activities of colonic mucosal and tumor PI-PLC (about 50%), but PEMC diet had no effect on phospholipase A₂. The production of 5(S)-, 8(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acids via the LOX pathway from arachidonic acid was reduced in colonic mucosa and tumors (30–60%) of animals fed the PEMC diet as compared to control diet. PEMC had no effect on the formation of colonic mucosal cyclooxygenase metabolites but inhibited the formation in colonic tumors by 15–30%. The precise mechanism by which PEMC inhibits colon tumorigenesis remains to be elucidated. It is likely that the chemopreventive action may be related, at least in part, to the modulation of PI-PLC-dependent signal transduction and LOX-mediated arachidonic acid metabolism.

¹ Supported by USPHS Grants CA 17613 and CA 44377 awarded by the National Cancer Institute.

² To whom requests for reprints should be addressed, at Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595.

Received 12/15/94. Accepted 4/ 4/95.

This article has been cited by other articles:

				N. Suh, S. Paul, X. Hao, B. Simi, H. Xiao, A. M. Rimando, and B. S. Reddy Pterostilbene, an Active Constituent of Blueberries, Suppresses Aberrant Crypt Foci Formation in the Azoxymethane-Induced Colon Carcinogenesis Model in Rats Clin. Cancer Res., January 1, 2007; 13(1): 350 - 355. [Abstract] [Full Text] [PDF]

				J. M.R. Patlolla, J. Raju, M. V. Swamy, and C. V. Rao {beta}-Escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21waf1/cip1 in colon cancer cells. Mol. Cancer Ther., June 1, 2006; 5(6): 1459 - 1466. [Abstract] [Full Text] [PDF]

				C. V. Rao, B. S. Reddy, V. E. Steele, C-X Wang, X. Liu, N. Ouyang, J. M.R. Patlolla, B. Simi, L. Kopelovich, and B. Rigas Nitric oxide-releasing aspirin and indomethacin are potent inhibitors against colon cancer in azoxymethane-treated rats: effects on molecular targets. Mol. Cancer Ther., June 1, 2006; 5(6): 1530 - 1538. [Abstract] [Full Text] [PDF]

				C. V. Rao, C. Indranie, B. Simi, P. T. Manning, J. R. Connor, and B. S. Reddy Chemopreventive Properties of a Selective Inducible Nitric Oxide Synthase Inhibitor in Colon Carcinogenesis, Administered Alone or in Combination with Celecoxib, a Selective Cyclooxygenase-2 Inhibitor Cancer Res., January 1, 2002; 62(1): 165 - 170. [Abstract] [Full Text] [PDF]

				N. N. Mahmoud, A. M. Carothers, D. Grunberger, R. T. Bilinski, M. R. Churchill, C. Martucci, H. L. Newmark, and M. M. Bertagnolli Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis Carcinogenesis, May 1, 2000; 21(5): 921 - 927. [Abstract] [Full Text] [PDF]

				C. V. Rao, T. Kawamori, R. Hamid, and B. S. Reddy Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor Carcinogenesis, April 1, 1999; 20(4): 641 - 644. [Abstract] [Full Text] [PDF]