Antitumor potential of dark sweet cherry sweet (Prunus avium) phenolics in suppressing xenograft tumor growth of MDA-MB-453 breast cancer cells

Abstract This study investigated in vivo the antitumor activity of dark sweet cherry (DSC) whole extracted phenolics (WE) and fractions enriched in anthocyanins (ACN) or proanthocyanidins (PCA) in athymic mice xenografted with MDA-MB-453 breast cancer cells. Mice were gavaged with WE, ACN, or PCA extracts (150 mg/kg body weight/day) for 36 days. Results showed that tumor growth was suppressed at similar levels by WE, ACN, and PCA compared to control group (C) without signs of toxicity or significant changes in mRNA oncogenic biomarkers in tumors or mRNA invasive biomarker in distant organs. Tumor protein analyses showed that WE, ACN, and PCA induced at similar levels the stress regulated ERK1/2 phosphorylation, known to be linked to apoptosis induction. However, ACN showed enhanced antitumor activity through downregulation of total oncogenic and stress-related Akt, STAT3, p38, JNK, and NF-kB proteins. In addition, immunohistochemistry analysis of Ki-67 revealed inhibition of tumor cell proliferation with potency WE ≥ ACN ≥ PCA. Differential quantitative proteomic high-resolution nano-HPLC tandem mass spectrometry analysis of tumors 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 differentially upregulated (P