Chemopreventive Potential of DSC Anthocyanins and Total Phenolics Extracted from Dark Sweet Cherry (DSC) Through Modulation of MDA-MB-453 Breast Tumor Proteomic Profile

OBJECTIVES: To investigate in vivo the chemopreventive activity of dark sweet cherry (DSC) extracted total phenolics (WE) or fractions enriched in anthocyanins (ACN) or proanthocyanidins (PCN) in athymic nude mice xenografted with MDA-MB-453 breast cancer cells. METHODS: MDA-MB-453 breast cancer cells (1 × 10(6) cells) were xenografted into athymic nude mice. Mice were gavaged with WE, ACN, or PCN extracts (150 mg/kg body weight/day) for 36 days followed by animal termination. Main organs and tumors were dissected for protein analyses following standard molecular biology techniques and high-resolution nano-HPLC tandem mass spectrometry. RESULTS: Tumor volume growth was suppressed at similar levels by WE, ACN, and PCN compared to controls (C) without signs of toxicity in main organs. Tumor protein analysis revealed ERK1/2 phosphorylation induced by WE, ACN, and PCN at similar levels, which may be linked to apoptosis induction by stress regulated ERK1/2 activation. Immunohistochemistry analysis showed decreased tumor cell proliferation and Ki-67 H-scores with potency WE ≥ ACN ≥ PCN. Differential quantitative proteomic analysis of tumor tissues from ACN and C groups revealed the identity of 71 proteins associated with poor breast cancer prognosis that were expressed only in C group (66 proteins), or upregulated in C group (5 proteins) compared to ACN group (p