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#B181 Orange Peel Extract Inhibits Intestinal Tumor Growth in ApcMin Mice.
Kunhua Fan, Naoto Kurihara, Sadanori Abe, Kan Yang, Martin Lipkin, Strang Cancer Prevention Center, New York, NY.
Epidemiological studies have indicated that components of fruits and vegetables reduce colon cancer risk.
Orange peel is a rich source of flavonoids with major constituents monomethoxyflavones and polymethoxyflavones, some reported to have antioxidant, anti-inflammatory and inducible nitric oxide synthase inhibitory activity.
An extract of orange peel (OPE) previously inhibited tumor development in CF1 mice after AOM (Ding et al. Food Factors, ACS Symposium 851, p213, 2003).
We have studied this extract of orange peel for its effect on intestinal tumor growth in a mouse model for human familial adenomatous polyposis.
ApcMin mice were fed one of 4 diets: (1) AIN-76A; (2) NWD (new Western-style diet, AIN-76A diet modified with decreased calcium, vitamin D, methyl donor nutrients and increased fat content); (3) NWD with OPE 0.25%; and (4) NWD with OPE 0.5% all premixed in diet.
After 9 weeks of feeding NWD to ApcMin mice the overall number of intestinal tumors per mouse increased 30% (48.4 vs. 37.1), 5.3-fold greater in colon (2.1 vs. 0.4, P<0.05) and 26% increased in small intestine (46.3 vs. 36.7, P>0.05) compared to AIN-76A controls.
In mice fed 0.5% OPE the overall number of tumors per mouse decreased 47% (25.5 vs. 48.4, P<0.02), with 48% decrease (24.0 vs. 46.3, P<0.01) in small intestine and 29% decrease (1.5 vs. 2.1, P>0.05) in colon compared to NWD group.
In mice fed 0.25% OPE a trend toward decreased tumor number of 26% (36.0 vs. 48.4), 25% (34.6 vs. 46.3) and 33% (1.4 vs. 2.1) was observed overall and in small intestine and colon respectively (P>0.05).
After feeding NWD the apoptotic index decreased 67% in flat mucosal crypts of small intestine and colon (0.003 vs. 0.009, P<0.001) and was 2.7-fold greater in tumors (0.019 vs. 0.007, P<0.001) compared to AIN-76A.
After feeding NWD with 0.5% OPE, the apoptotic index increased 100% in flat mucosal crypts of small intestine and colon (0.006 vs. 0.003, P<0.02), and increased 58% in tumors (0.030 vs. 0.019, P<0.001) compared to NWD.
These findings demonstrate that NWD increased intestinal tumor development in a preclinical mouse model of human FAP, and OPE significantly decreased tumor development in the intestine of this model in association with modulation of apoptosis in flat intestinal mucosa and in tumors.
Frontiers in Cancer Prevention Research, 2003
AACR
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