Obesity is known to be a risk factor for colon
carcinogenesis. Although there are several reports on the chemopreventive abilities of dietary
flavonoids in chemically induced colon
carcinogenesis, those have not been addressed in an
obesity-associated
carcinogenesis model. In the present study, the effects of 3
flavonoids (
chrysin,
quercetin and
nobiletin) on modulation of the occurrence of putative preneoplastic lesions,
aberrant crypt foci (ACF), and
beta-catenin-accumulated crypts (BCACs) in the development of
colon cancer were determined in male db/db mice with
obesity and diabetic phenotypes. Male db/db mice were given 3 weekly
intraperitoneal injections of
azoxymethane (AOM) to induce the ACF and BCAC. Each
flavonoid (100ppm), given in the diet throughout the experimental period, significantly reduced the numbers of ACF by 68-91% and BCAC by 64-71%, as well as proliferation activity in the lesions. Clinical chemistry results revealed that the serum levels of
leptin and
insulin in mice treated with AOM were greater than those in the untreated group. Interestingly, the most pronounced suppression of development of preneoplastic lesions and their proliferation were observed in the
quercetin-fed group, in which the serum
leptin level was lowered. Furthermore,
quercetin-feeding decreased
leptin mRNA expression and secretion in differentiated 3T3-L1 mouse adipocytes. These results suggest that the present dietary
flavonoids are able to suppress the early phase of colon
carcinogenesis in obese mice, partly through inhibition of proliferation activity caused by serum
growth factors. Furthermore, they indicate that certain
flavonoids may be useful for prevention of colon
carcinogenesis in obese humans.