Dietary intake of rosmarinic acid by Apc(Min)  mice, a model of colorectal carcinogenesis: levels of parent agent in the target tissue and effect on adenoma development.
METHODS
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 Apc(Min) mouse model of colorectal carcinogenesis, and to correlate efficacy with levels of RA achieved in the plasma and gastrointestinal tract.


RESULTS
RA inhibited the growth of APC10.1 cells derived from Apc(Min) mouse adenomas, with an IC₅₀ of 43 μM. Consumption of dietary RA (0.3%) by Apc(Min) mice for 8 weeks post weaning decreased adenoma burden by ∼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 μM and 38 nmol/g, respectively.


CONCLUSIONS
Chronic consumption of RA furnished quantifiable levels of parent compound in the plasma and intestinal tract of Apc(Min) mice and may slow adenoma development.
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
Ankur
A
Karmokar
Timothy H
TH
Marczylo
Hong
H
Cai
William P
WP
Steward
Andreas J
AJ
Gescher
Karen
K
Brown
D000236:Adenoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002934:Cinnamates / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D053630:Depsides / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D017491:Genes, APC; D007413:Intestinal Mucosa / Q000187:drug effects; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D000097123:Rosmarinic Acid
D016588:Anticarcinogenic Agents; D002934:Cinnamates; D053630:Depsides; D000097123:Rosmarinic Acid