Suppression of colon carcinogenesis by bioactive compounds in grapefruit
J Vanamala, T Leonardi, BS Patil, SS Taddeo… - …, 2006 - academic.oup.com
Carcinogenesis, 2006•academic.oup.com
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,
137 Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg) …
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,
137 Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg) …
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, 137 Cs) 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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