Dietary Berries and Ellagic Acid Diminish Estrogen-Mediated Mammary Tumorigenesis ∈ ACI rats

Abstract

Estrogen acts as a complete mammary carcinogen in ACI rats. Prevention studies in this model allowed us to identify agents that are effective against estrogen-induced mammary carcinogenesis. In this study, we investigated efficacy of dietary berries and ellagic acid to reduce estrogen-mediated mammary tumorigenesis. Female ACI rats (8–9 wk) were fed either AIN-93M diet (n = 25) or diet supplemented with either powdered blueberry (n = 19) and black raspberry (n = 19) at 2.5% wt/wt each or ellagic acid (n = 22) at 400 ppm. Animals received implants of 17β-estradiol 2 wk later, were palpated periodically for mammary tumors, and were euthanized after 24 wk. No differences were found in tumor incidence at 24 wk; however, tumor volume and multiplicity were reduced significantly after intervention. Compared with the control group (average tumor volume = 685 ± 240 mm3 and tumor multiplicity = 8.0 ± 1.3), ellagic acid reduced the tumor volume by 75% (P < 0.005) and tumor multiplicity by 44% (P < 0.05). Black raspberry followed closely, with tumor volume diminished by > 69% (P < 0.005) and tumor multiplicity by 37% (P = 0.07). Blueberry showed a reduction (40%) only in tumor volume. This is the first report showing the significant efficacy of both ellagic acid and berries in the prevention of solely estrogen-induced mammary tumors.

ACKNOWLEDGMENTS

This work was supported from the United States Public Health Service Grants CA–90892 and CA–92758 and in part from the Agnes Brown Duggan Foundation. H. S. Aiyer was supported in part by graduate fellowship from the Graduate Center for Nutritional Sciences, University of Kentucky. We gratefully acknowledge Dr. Manicka Vadhanam for his assistance in establishing the ACI rat model in the laboratory; Drs. Srivani Ravoori and Sunati Sahoo for assistance with the histology, and Dr. Barb Mickelson of Harlan Teklad for assistance in planning isocaloric diets. We also express our sincere thanks to Dr. James Shull of the University of Nebraska for many useful discussions during the course of this study.

Notes

^a In the study, 7-to 8-wk-old animals were received and maintained initially on AIN-93M control diet for a week followed by experimental diets for another 2 wk before 17β-estradiol implantation. Animals were maintained on experimental diets until the end of the study.

^a Animals were euthanized after 24 wk of estrogen treatment. Organ wet weights were measured after excision. Tumor volume was calculated as the volume of a spheroid (2/3 π r1*r2*r3). Values denote mean ± standard error of measurement. “n” designates only those animals that survived 24 wk. All comparisons are between control diet and respective diets.