Carcinogenesis Advance Access originally published online on December 29, 2005
Carcinogenesis 2006 27(6):1257-1265; doi:10.1093/carcin/bgi318
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Suppression of colon carcinogenesis by bioactive compounds in grapefruit
1 Department of Nutrition and Food Science, 2 Vegetable and Fruit Improvement Center, Department of Horticultural Sciences and 3 Department of Statistics, Texas A&M University, College Station, TX-77843, USA
* To whom correspondence should be addressed. Tel: +1 979-847-8714; Fax: +1 979-862-1862; Email: n-turner{at}tamu.edu
This study evaluated the hypothesis that untreated and irradiated grapefruit as well as the isolated citrus compounds naringin and limonin would protect against azoxymethane (AOM)-induced aberrant crypt foci (ACF) by suppressing proliferation and elevating apoptosis through anti-inflammatory activities. Male Sprague–Dawley rats (n = 100) were provided one of five diets: control (without added grapefruit components), untreated or irradiated (300 Gy, 137Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg). Rats were injected with saline or AOM (15 mg/kg) during the third and fourth week and colons were resected (6 weeks post second injection) for evaluation of ACF, proliferation, apoptosis, and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein levels. Experimental diets had no effect on the variables measured in saline-injected rats. However, in AOM-injected rats, the experimental diets suppressed (P 
0.02) aberrant crypt and high multiplicity ACF (HMACF; P 0.01) formation and the proliferative index (P 0.02) compared with the control diet. Only untreated grapefruit and limonin suppressed (P 0.04) HMACF/cm and expansion (P 0.008) of the proliferative zone that occurred in the AOM-injected rats consuming the control diet. All diets elevated (P 0.05) the apoptotic index in AOM-injected rats, compared with the control diet; however, the greatest enhancement was seen with untreated grapefruit and limonin. Untreated grapefruit and limonin diets suppressed elevation of both iNOS (P 0.003) and COX-2 (P 0.032) levels observed in AOM-injected rats consuming the control diet. Although irradiated grapefruit and naringin suppressed iNOS levels in AOM-injected rats, no effect was observed with respect to COX-2 levels. Thus, lower levels of iNOS and COX-2 are associated with suppression of proliferation and upregulation of apoptosis, which may have contributed to a decrease in the number of HMACF in rats provided with untreated grapefruit and limonin. These results suggest that consumption of grapefruit or limonin may help to suppress colon cancer development.
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