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 down-regulation 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 66 proteins associated with poor breast cancer prognosis that were expressed only in C group (61 proteins) or differentially up-regulated (P<.05) in C group (5 proteins). These findings revealed ACN-targeted proteins associated to tumor growth and invasion and the potential of DSC ACN for breast cancer treatment. Results lead to a follow-up study with highly immunodeficient mice/invasive cell line subtype and advanced tumor development to validate the anti-invasive activity of DSC anthocyanins.

这项研究在体内研究了黑甜樱桃（DSC）整体提取的酚类（WE）和富含花青素（ACN）或原花色素（PCA）的级分在异种移植了MDA-MB-453乳腺癌细胞的无胸腺小鼠中的抗肿瘤活性。用WE，ACN或PCA提取物（150 mg / kg体重/天）灌胃36天。

结果表明，与对照组（C）相比，WE，ACN和PCA抑制了肿瘤的生长，但无毒性迹象或肿瘤中的mRNA致癌生物标志物或远处器官的mRNA侵入性生物标志物没有明显变化。肿瘤蛋白分析表明，WE，ACN和PCA在相似水平下诱导了应激调节的ERK1 / 2磷酸化，已知与细胞凋亡的诱导有关。但是，ACN通过下调总的致癌和应激相关的Akt，STAT3，p38，JNK和NF-kB蛋白显示出增强的抗肿瘤活性。另外，Ki-67的免疫组织化学分析显示，效力WE≥ACN≥PCA抑制了肿瘤细胞的增殖。C组（5种蛋白质）中P <.05）。这些发现揭示了靶向ACN的蛋白与肿瘤的生长和侵袭有关，以及DSC ACN在乳腺癌治疗中的潜力。结果导致对高度免疫缺陷的小鼠/侵袭性细胞系亚型和晚期肿瘤发生的后续研究，以验证DSC花色苷的抗侵袭活性。