Suppression of early colon cancer lesions by apigenin and naringenin is in part due to their downregulation of p21, TLR‐4, and MCT‐1 expression

We have shown that apigenin and naringenin (flavonoids) suppress colon carcinogenesis by inducing apoptosis and suppressing proliferation in rats. The goal of this experiment was to test the hypothesis that apigenin and naringenin affect proliferation and apoptosis by regulating expression of genes involved in microbial recognition (TLR‐2, TLR‐4), short‐chain fatty acid transport (MCT‐1), cell cycle (p21), and apoptosis (Bax, Bcl‐2, Fas). Rats received diets (0.02% naringenin, 0.1% apigenin, or control) for 10 wk and were treated with AOM at wk 3 and 4. Apigenin suppressed (p<0.05) MCT‐1 expression compared to control, with naringenin being intermediate. Apigenin and naringenin suppressed (p<0.01) p21 expression. Expression of TLR‐4, a promoter of proliferation, also was suppressed by apigenin and naringenin (p<0.04). Diet did not affect expression of Bax, Bcl‐2, Fas, or TLR‐2. Considering MCT‐1 is a butyrate transporter and butyrate induces colonocyte p21 expression, it is possible that suppression of p21 by apigenin and naringenin may be a MCT‐1 mediated effect. Reduction of MCT‐1, p21, and TLR‐4 expression by apigenin and naringenin could have contributed to apoptosis induction and suppression of proliferation. Thus, both apigenin and naringenin were able to reduce colon carcinogenesis through their influence on expression of genes involved in multiple pathways. Funding USDA 2010‐34402‐20875.