Anthocyanin-rich red grape extract impedes adenoma development in the Apc(Min) mouse: pharmacodynamic changes and anthocyanin levels in the murine biophase.
OBJECTIVE
Red grape pomace extract (oenocyanin) is a cheap and rich source of anthocyanins, the agents suggested to possess cancer chemopreventive properties. Here the hypothesis was tested that oenocyanin added to the diet can interfere with intestinal adenoma development in the Apc(Min) mouse, a model of intestinal carcinogenesis linked to an Apc mutation.


METHODS
Mice received oenocyanin (0.3%) in their diet until week 16, when adenoma number and burden were recorded. Expression of Akt and ERK proteins was studied by Western blot in adenomas to discover effects of anthocyanins on cellular signalling via the PI3 and MAP kinase pathways. Levels of anthocyanins were measured by HPLC with visible spectroscopic or mass spectrometric detection.


RESULTS
In mice which had consumed oenocyanin, overall adenoma burden was halved and adenoma number was marginally reduced when compared with mice on control diet. The proliferation index in colonic adenomatous crypts, as reflected by Ki-67 staining, was significantly decreased from 88.14% in control mice to 75.6+/-4% in mice on oenocyanin (P=0.014). Expression of Akt in small intestinal adenomas from Apc(Min) mice on oenocyanin was reduced by 54% (P=0.003), when compared to controls. Oenocyanin anthocyanins and glucuronide metabolites were found in the urine and intestine but not in plasma.


CONCLUSIONS
The results suggest that oenocyanin may be a viable and economical alternative to anthocyanin-rich berry extracts for chemopreventive intervention. Akt and pErk might be suitable biomarkers of anthocyanin target organ efficacy.
Cai
Hong
H
Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
Marczylo
Timothy H
TH
Teller
Nicole
N
Brown
Karen
K
Steward
William P
WP
Marko
Doris
D
Gescher
Andreas J
AJ
D000236:Adenoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000872:Anthocyanins / Q000032:analysis* / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*; D019892:eIF-2 Kinase / Q000378:metabolism
D000872:Anthocyanins; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D019892:eIF-2 Kinase