Dietary intake of rosmarinic acid by ApcMin mice, a model of colorectal carcinogenesis: levels of parent agent in the target tissue and effect on adenoma development.

摘要

Scope. Rosmarinic acid (RA), a constituent of culinary herbs is considered to possess cancer chemopreventive properties. It has been shown to inhibit the development of cancer in preclinical models but data are conflicting and whether it can protect against gastrointestinal malignancies in vivo has not been examined. This study aimed to investigate the effect of RA on the development of intestinal adenomas in the ApcMin mouse model of colorectal carcinogenesis, and to correlate efficacy with levels of RA achieved in the plasma and gastrointestinal tract. Methods and results. RA inhibited the growth of APC10.1 cells derived from ApcMin mouse adenomas, with an IC₅₀ of 43 muM. Consumption of dietary RA (0.3%) by ApcMin mice for 8 weeks post weaning decreased adenoma burden by approx. 35%, but the difference from controls was not significant. Although RA significantly decreased the frequency of large adenomas, the number of small ones increased. Using a novel validated HPLC assay, average levels of RA in the plasma and intestinal mucosa of these mice were found to be 1.1 muM and 38 nmol/g, respectively. Conclusion. Chronic consumption of RA furnished quantifiable levels of parent compound in the plasma and intestinal tract of ApcMin mice and may slow adenoma development