Berries and Ellagic Acid Prevent Estrogen-Induced Mammary Tumorigenesis by Modulating Enzymes of Estrogen Metabolism

Abstract

To determine whether dietary berries and ellagic acid prevent 17β-estradiol (E 2 )-induced mammary tumors by altering estrogen metabolism, we randomized August-Copenhagen Irish rats (n = 6 per group) into five groups: sham implant + control diet, E 2 implant + control diet (E 2 -CD), E 2 + 2.5% black raspberry (E 2 -BRB), E 2 + 2.5% blueberry (E 2 -BB), and E 2 + 400 ppm ellagic acid (E 2 -EA). Animals were euthanized at early (6 wk), intermediate (18 wk), and late (24 wk) phases of E 2 carcinogenesis, and the mammary tissue was analyzed for gene expression changes using quantitative real-time PCR. At 6 weeks, E 2 treatment caused a 48-fold increase in cytochrome P450 1A1 (CYP1A1; P < 0.0001), which was attenuated by both BRB and BB diets to 12-and 21-fold, respectively (P < 0.001). E 2 did not alter CYP1B1 levels, but both berry and EA diets significantly suppressed it by 11-and 3.5-fold, respectively, from baseline (P < 0.05). There was a 5-fold increase in 17β-hydroxysteroid dehydrogenase 7 (17βHSD7), and this was moderately abrogated to ∼2-fold by all supplementation (P < 0.05). At 18 weeks, CYP1A1 was elevated by 15-fold in E 2 -CD and only E 2 -BB reduced this increase to 7-fold (P < 0.05). Catechol-O-methyltransferase expression was elevated 2-fold by E 2 treatment (P < 0.05), and all supplementation reversed this. At 24 weeks, CYP1A1 expression was less pronounced but still high (8-fold) in E 2 -treated rats. This increase was reduced to 3.2-and 4.6-fold by E 2 -BRB and E 2 -EA, respectively (P < 0.05), but not by E 2 -BB. Supplementation did not alter the effect of E 2 on steroid receptors. The diets also significantly suppressed mammary tumor incidence (10-30%), volume (41-67%), and multiplicity (38-51%; P < 0.05). Berries may prevent mammary tumors by suppressing the levels of E 2 -metabolizing enzymes during the early phase of E 2 carcinogenesis. Cancer Prev Res; 3(6); 727-37. ©2010 AACR.

Lung cancer inhibitory activity of dietary berries and berry polyphenolics

“…This study also demonstrated that the anthocyanin fraction of black raspberries (BRB) was as effective in preventing chemically-induced esophageal tumors in rats as whole BRB powder [6]. Our own studies have shown significant inhibition of breast cancer in the rat model by both blueberry (BB) and BRB, indicating that berries are chemopreventive beyond the GI tract [7][8][9]. Our studies with BB diet have also shown that berry anthocyanidins are bioavailable beyond the GI as we could detect all anthocyanidins in lung tissues [10].…”

“…For the preparations of the BB and BRB diet, AIN 93M diet was powdered and mixed with BB and BRB powder at 5% and 2.5% (w/w), respectively, and stored at 4 • C until use. The diets were isocaloric and the recipe used was the same as described by us elsewhere [8,16,17].…”

Anti-metastasis Activity of Black Rice Anthocyanins Against Breast Cancer: Analyses Using an ErbB2 Positive Breast Cancer Cell Line and Tumoral Xenograft Model

“…Anthocyanins are abundant flavonoid constituents existing in colorful fruits and vegetables. It is reported that anthocyanins enriched foods can inhibit the development of cancer in carcinogen treated animals and in animals with a hereditary predisposition to cancer (Aiyer et al, 2010;Stoner et al, 2010).As shown in this study, the effective dose was much higher than normal chemical clinic medication mainly due to the low abundance of active ingredients in BRACs, poor absorption and rapid degradation of anthocyanins in gastrointestinal tract (Dreiseitel et al, 2009;Forester et al, 2010).…”

Phytonutrients from Fruits and Vegetables in Breast Cancer Control

“…26 It was revealed by another study that supplementation of HER2/neu-overexpressing transgenic mice with resveratrol delayed spontaneous mammary tumor development and reduced metastasizing capacity by downregulating the expression of HER2/ neu and induction of apoptosis in tumor cells. 42 Ellagic acid present in berries was reported to significantly reduce the breast cancer burden on rats according to a study conducted in 2010 by Aiyer et al 43 The induction of breast cancer was associated with increase in a number of metabolic enzymes including cytochrome P450, 17β-HSD, and catechol-O-methyltransferase. The flavonoid quercetin has been reported to show apoptotic activities in breast tumors in vivo.…”