Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats

Abstract

The modifying effect of dietary administration of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received diets containing 100 or 500 p.p.m. auraptene for 5 weeks, starting 1 week before the first dose of AOM. At termination of the study (week 5) dietary administration of auraptene caused a significant reduction in the frequency of ACF in a dose-dependent manner (P < 0.05). Feeding of auraptene suppressed expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling-index, ornithine decarboxylase activity, polyamine content and number of silver stained nucleolar organizer region protein particles) in the colonic mucosa and the occurrence of micronuclei caused by AOM. Also, auraptene increased the activities of phase II enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings might suggest that inhibition of AOM-induced ACF may be associated, in part, with increased activity of phase II enzymes in the liver and colon and suppression of cell proliferation in the colonic mucosa.

Prenylation of Aromatic Secondary Metabolites: A New Frontier for Development of Novel Drugs

“…These findings indicate that the prenyl group is an important structural feature for good anti tumor promoting activity of the acridone molecule and can be exploited in new drug development. [15]. Another natural occurring prenyloxy coumarin is umbelliprenin (7-trans, trans-farnesyloxy coumarin) (12), isolated from Ferula persica [16].…”

Prevention of Colonic Aberrant Crypt Foci by Dietary Feeding of Chalcone and 2-Hydroxychalcone in Male F344 Rats.

“…Several other colon tumor inhibitors have been shown to interact with AOM metabolism and inhibit AOM carcinogenicity 34 . In this study, chalcone and 2OH-chalcone induced phase II detoxification enzymes, GST and QR, in the liver and colon, as did auraptene 21 and organosulfur compounds 35 . Moreover chalcone derivatives were potent and selective inhibitors of cytochrome P450 36 .…”

“…The frequency of ACF was determined according to the method described in our previous report 21 . At necropsy, the colons were flushed with saline, excised, cut open longitudinally along the main axis, and then washed with saline.…”

“…A total of 35 rats were used to assay GST and QR activities of liver and colorectal mucosa according to the method described previously 21 . Animals were daily gavaged with chalcone or 2OH-chalcone at a dose of 0, 40, 200 or 400 mg/kg body weight for 5 consecutive days.…”

Lack of Enhancing Effect of Lauric Acid on the Development of Aberrant Crypt Foci in Male ICR Mice Treated with Azoxymethane and Dextran Sodium Sulfate

“…The number of ACF per colon was determined according to the method described in our previous report 44 . At necropsy, the length (from the ileocecal junction to the anal verge) of the large bowel was measured.…”