Carnosic acid suppresses colon tumor formation in association with antiadipogenic activity

Scope: This study determined the efficacy of carnosic acid (CA) for suppressing colon carcinogenesis associated with excess adiposity. Methods and results: Cell growth regulation by CA was evaluated in HT-29 colon adenocarcinoma cells cocultured with 3T3-L1 adipocytes. To determine the in vivo efficacies, male A/J mice were divided into four groups and fed one of the following experimental diets for 11 wk: 15% fat, 45% fat, 45% fat + 0.01% CA, or 45% fat + 0.02% CA. Azoxymethane was administered at the beginning of experimental diet and two cycles of dextran sodium sulfate were supplied 1 wk after the azoxymethane injection. The proliferation of HT-29 cells cocultured with 3T3-L1 cells was significantly higher than proliferation of control cells (p < 0.05). CA treatment suppressed the growth of cocultured HT-29 cells through cell cycle arrest and enhanced apoptosis by inhibiting leptin receptor (Ob-R) signaling, including Akt and extracellular signal-regulated kinase (ERK) phosphorylation. CA supplementation in vivo decreased the number of colon tumors and reduced circulating concentrations of leptin, adiponectin, insulin, and insulin-like growth factor 1. Colonic expression of Ob-R, insulin receptor (IR), p-Akt, p-ERK, B-cell lymphoma extra large (Bcl-xL), and cyclinD1 protein was also suppressed in animals fed CA. Conclusion: CA appears to alleviate adipocity-related acceleration of colon tumor formation.