Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers in pre-clinical studies. In our earlier studies, blueberry-supplemented diet has shown chemopreventive protection against 17β-estradiol-mediated mammary tumorigenesis. The 5 anthocyanidins in blueberry are presumable bioactives. In this study, we tested both preventive and therapeutic activities of high anthocyanin-content blueberry diet in ACI rat model against 17β-estradiol-mediated mammary tumorigenesis. The blueberry used was a blend of Tifblue and Rubel blueberry (50:50) (U.S. Highbush Blueberry Council, CA) which has substantially higher amount of anthocyanins than Berkley/Blue Jay/Bluecrop blueberries used in our earlier studies. To study the chemopreventive effect, female ACI rats (5-6-week old) were administered AIN-93M diet or diets supplemented with blueberry (2.5 and 5%, w/w) 2 weeks prior to 17β-estradiol implantation. To test for the therapeutic activity, when 5% of the animals in the control group developed palpable tumors, one half of the animals were provided diet supplemented with 5% blueberry while the other half were continued on control diet. Animals received diet and water ad libitum and palpated weekly to determine the effect of berry intervention on tumor latency and tumor growth. When the tumor incidence reached >90% in estrogen-treated group on control diet, all the animals were euthanized. Our data revealed i) the first tumor in control group appeared after 85 days, while this was delayed by 28 and 37 days in groups receiving 5% blueberry in chemopreventive and therapeutic mode, respectively. The effect was less pronounced (delay by 7 days) with 2.5% berry; ii) the tumor incidence was also decreased dose dependently (96% in control versus 85% and 61% with 2.5% and 5% blueberry in chemopreventive mode, 55% with 5% blueberry in therapeutic mode); iii) a 25% and 51% reduction in tumor multiplicity with 2.5% and 5% blueberry, respectively (57% reduction with 5% blueberry in therapeutic mode); and iv) 37% and 45% reduction in tumor volume with 5% blueberry in chemopreventive and therapeutic modes, respectively; the effect with 2.5% blueberry was only modest. These data suggest that the test blueberry is effective in inhibiting estrogen-mediated mammary tumorigenesis in both chemopreventive and therapeutic modes. In view of our recent findings of miRNA ‘signature’ in estrogen-induced mammary tumors and its favorable modulation by ellagic acid, we are analyzing modulation of miRNAs in the current study and its correlation with the tumor inhibition. (Supported by Highbush Blueberry Council, CA, Agnes Brown Duggan Fund and Helmsley Foundation).
Citation Format: Jeyaprakash Jeyabalan, Farrukh Aqil, Radha Munagala, Ramesh Gupta. Chemopreventive and therapeutic activity of high anthocyanin-content blueberry against estrogen-mediated breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3705. doi:10.1158/1538-7445.AM2013-3705