Pre-clinical development of anthocyanins as colorectal cancer chemopreventive agents

The hypothesis was tested that dietary Mirtoselect, a standardised mixture of 15 anthocyanins, or the isolated anthocyanin cyanidin-3-glucoside (C3G) affect adenoma development in the ApcMIN mouse, a genetic model of colorectal cancer. Anthocyanins were added to the diet at 0.03, 0.1 or 0.3% (w/w) for the animals' life time. Adenoma number and size were measured at the end of the experiment (week 16). Both interventions reduced adenoma number/burden in a dose-dependent fashion. A potential mechanism by which anthocyanins are thought to exert cancer chemoprevention is anti-oxidation. Anti-oxidant effects of the interventions were investigated in DNA from ApcMIN murine adenoma tissue by analysis of the pyrimidopurinone adduct of deoxyguanosine M1dG, a product of the reaction of DNA with malondialdehyde. At the dietary dose of 0.3% C3G and Mirtoselect significantly reduced levels of M1dG, suggesting that antioxidation may contribute to anthocyanin-mediated interference with adenoma development. C57BL mice, the ApcMIN background strain, received C3G po or I.V. at 500 or 1 mg/kg, respectively. Levels of anthocyanins in plasma and tissue were measured using a newly developed HPLC method. C3G bioavailability was 3.28%, consistent with literature values after ingestion of berries/fruits. Anthocyanin species were detected in the plasma, urine, mucosa, liver, kidneys, heart, lung, gall bladder and brain. Absorption, distribution and excretion in the urine were rapid. The mean time of peak levels for all tissues studied was ∼26 min. The work described here defines further the potential role of anthocyanins in colorectal cancer chemoprevention. It also describes pharmacokinetic and pharmacodynamic features which may help optimise future clinical chemoprevention trials.