Abstract 1887: Distinct molecular targets of blueberry and black raspberry in breast cancer prevention

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Abstract We previously demonstrated protection with berries in diet, against estrogen-induced ACI rat mammary tumorigenesis, by inhibition of proliferation as early as 3 weeks of estrogen administration. In this study, blueberry (BB) and black raspberry (BRB) were administered in diet at 5% 2 weeks prior to implantation with 1.2 cm silastic implants containing 9 mg 17β-estradiol. Rats were killed at 3 weeks, 3 months and ∼7 months, when the tumor incidence in control group reached 80%. Analysis revealed significant reduction (p<0.05) in tumor volume (Control: 801.2±105.3 mm3; BB: 395±97.9 mm3; BRB: 461±109.8 mm3) and tumor multiplicity (Control: 6.9±0.9; BB: 4.4±0.6; BRB: 4.3±0.6) by the berry diets. Most important finding is that while BB was more effective in reducing the tumor volume, BRB was more efficient in delaying the first tumor incidence, by 5 weeks (p<0.05). We also investigated the key molecules of cell-cycle regulation, cell proliferation and transcription. The cell-cycle regulatory molecule cyclin D1 which was up-regulated by 3-4-fold in mammary tissues with estrogen treatment, was significantly down-regulated by BB diet as early as 3 weeks and remained down-regulated during the entire tumorigenesis period (p<0.05), as detected by western blot. BRB diet did not show any significant down-regulation of cyclin D1. Estrogen receptor α, on the other hand, which was significantly overexpressed with estrogen treatment at all the three time points, was significantly offset by BRB diet, but it was not well pronounced with BB diet. Molecules downstream of these effector proteins are currently being explored. While BB contains five distinct anthocyanidins (delphinidin, cyanidin, malvidin, peonidin, and petunidin) and insignificant levels of ellagic acid, BRB contains chiefly cyanidin and high levels of ellagic acid. Thus, the distinct and specific molecular targets and pathways involved in the protective actions of the two berries corroborate their distinct phytochemical signatures. (Supported by CA-118114 and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1887.