| dc.description.abstract | Colon cancer is the third most common cancer in the United States. However,
evidence indicates that a proper diet abundant in fruits and vegetables may be protective
against colon cancer development. Bioactive compounds in fruits and vegetables, such
as flavonoids and limonoids, have been shown to possess anti-proliferative and antitumorigenic
effects in various in vitro and in vivo models of cancer. Since there are few
animal studies involving flavonoids and limonoids and colon cancer, this experiment
investigated the potentially protective effects of four citrus flavonoids and one limonoid
mixture against the promotion stage of chemically-induced colon cancer in rats. Male
SD rats (n =60; 10 rats/group) were assigned to receive diets containing 0.1% apigenin,
0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin
glucoside/obacunone glucoside mixture, or a control diet (0% flavonoid/limonoid). Rats
received the diets for 10 wk and were injected with azoxymethane (15 mg/kg) at wk 3
and 4. The excised colons were evaluated for aberrant crypt foci (ACF) formation, cell
proliferation (PCNA assay), apoptosis (TUNEL assay), and iNOS and COX-2
expression. When compared to the control diet, apigenin lowered the number of high
multiplicity ACF (> 4 AC/focus) by 57% (P<0.05) and tended to lower the proliferative
index (28%; P=0.07), while naringenin lowered both the number of high multiplicity
ACF by 51% (P<0.05) and the proliferative index by 32% (P<0.05). Both apigenin and
naringenin increased apoptosis of surface colon cells (78% and 97%, respectively;
P<0.05) when compared to control diet. Hesperidin, nobiletin, and the limoninglucoside/obacunone glucoside mixture did not have any effects on the above variables
measured in this model of colon carcinogenesis. The colonic mucosal protein levels of
iNOS or COX-2 were not different among the six diet groups. Evidence suggests that
high multiplicity ACF are indicative of future tumor development in both humans and
rats. Furthermore, dysregulated proliferation and apoptosis may also lead to
tumorigenesis. Therefore, the ability of dietary apigenin and naringenin to reduce high
multiplicity ACF, lower proliferation, and increase apoptosis may contribute toward
colon cancer prevention. However, their protection is not due to their influence on iNOS
and COX-2 protein levels. | en |
