Inhibitory Effects of Oral Administration of an Extract of Orange Peel in the Diet on Azoxymethane-Induced Formation of Aberrant Crypt Foci and Colon Tumor in CF-1 Mice

摘要

Orange peel possesses antioxidant and anti-inflammatory activity and preventive cancer activity. We have evaluated the effect of an extract of orange peel on azoxymethane (AOM)-induced formation of aberrant crypt foci and colon tumor in CF-1 mice. An extract of orange peel contains approximately 30% polymethoxyflavones. Female CF-1 (6 weeks old) that were s.c. injected with AOM (5, 10, 10, and 10 mg/Kg body weight) once every 4 days resulted in formation of an average of 5.2 aberrant crypt foci (ACF) per colon and 37 aberrant crypt (AC) per colon at 24 weeks after the first dose of AOM treatment. Feeding 0.2% orange peel extract in the AIN 76A diet to mice starting at 2 weeks before the first dose of AOM until the end of the experiment inhibited AOM-induced formation of the number of ACF per colon and AC per colon by 48% and 66% respectively. Feeding 0.2% norhydroxyguaiaretic acid (NDGA), an inhibitor of lipoxygenase, in the AIN 76A diet to mice during both the initiation and promotion phases inhibited the number of AOM-induced formation of ACF per colon and AC per colon by 48% and 75% respectively. Mice developed an average of 0.52 colon tumors per mouse and 44% of mice had colon tumors after 37 weeks of the first dose of AOM injection. The number of AOM-induced colon tumors was decreased by 44% or 48%, when 0.2% orange peel in AIN 76A diet or 0.2% nordihydroxguaiaretic acid in AIN 76A diet was used to replace the control AIN 76A diet. Feeding 0.2% orange peel diet or 0.2% nordihydroxyguaiaretic acid diet also decreased colon tumor incidence by 34% or 39%, respectively.