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Suppression of colon carcinogenesis by bioactive compounds in grapefruit
Jairam Vanamala1, Tety Leonardi, Bhimanagouda S Patil
1Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
Abstract:
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 < or = 0.02) aberrant crypt and high multiplicity ACF (HMACF; P < or = 0.01) formation and the proliferative index (P < or = 0.02) compared with the control diet. Only untreated grapefruit and limonin suppressed (P < or = 0.04) HMACF/cm and expansion (P < or = 0.008) of the proliferative zone that occurred in the AOM-injected rats consuming the control diet. All diets elevated (P < or = 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 < or = 0.003) and COX-2 (P < or = 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.
Insights
Grapefruit and limonin show promise in preventing colon cancer by reducing aberrant crypt foci and inflammation. These natural compounds may suppress cancer development by lowering proliferation and increasing apoptosis.
Area of Science:
- Nutritional Science
- Cancer Research
- Biochemistry
Background:
- Aberrant crypt foci (ACF) are early indicators of colon cancer.
- Citrus compounds like naringin and limonin are being investigated for chemopreventive properties.
- Inflammation, proliferation, and apoptosis play critical roles in cancer development.
Purpose of the Study:
- To evaluate the protective effects of grapefruit and its compounds against azoxymethane (AOM)-induced ACF in rats.
- To investigate the mechanisms underlying these effects, including modulation of proliferation, apoptosis, and inflammatory markers (COX-2, iNOS).
Main Methods:
- Male Sprague-Dawley rats were fed diets containing control, untreated grapefruit, irradiated grapefruit, naringin, or limonin.
- Azoxymethane (AOM) was administered to induce ACF.
- Colon tissues were analyzed for ACF, proliferation, apoptosis, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) levels.
Main Results:
- Experimental diets, particularly untreated grapefruit and limonin, significantly suppressed ACF and high multiplicity ACF (HMACF) formation.
- Untreated grapefruit and limonin diets reduced the proliferative index and expansion of the proliferative zone.
- All tested diets increased the apoptotic index, with the most significant increase observed with untreated grapefruit and limonin.
- Untreated grapefruit and limonin diets suppressed the elevation of iNOS and COX-2 levels induced by AOM.
Conclusions:
- Untreated grapefruit and limonin demonstrate significant chemopreventive effects against AOM-induced colon cancer in rats.
- These effects are associated with suppressed proliferation, elevated apoptosis, and reduced inflammatory markers (iNOS and COX-2).
- Consumption of grapefruit or limonin may contribute to the suppression of colon cancer development.
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