syringin and Breast-Neoplasms

Breast cancer (BC) is one of the most common malignant tumors with the highest mortality in the world. Modern pharmacological studies have shown that Syringin has an inhibitory effect on many tumors, but its anti-BC efficacy and mechanism are still unclear.. First, Syringin was isolated from Acanthopanax senticosus (Rupr. & Maxim.) Harms (ASH) by systematic solvent extraction and silica gel chromatography column. The plant name is composed of genus epithet, species additive words and the persons' name who give its name. Then, the hub targets of Syringin against BC were revealed by bioinformatics. To provide a more experimental basis for later research, the hub genes which could be candidate biomarkers of BC and a ceRNA network related to them were obtained. And the potential mechanism of Syringin against BC was proved in vitro experiments.. Syringin was obtained by liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC). Bioinformatics results showed that MAP2K1, PIK3CA, HRAS, EGFR, Caspase3, and PTGS2 were the hub targets of Syringin against BC. And PIK3CA and HRAS were related to the survival and prognosis of BC patients, the PIK3CA-hsa-mir-139-5p-LINC01278 and PIK3CA-hsa-mir-375 pathways might be closely related to the mechanism of Syringin against BC. In vitro experiments confirmed that Syringin inhibited the proliferation and migration and promoted apoptosis of BC cells through the above hub targets.. Syringin against BC via PI3K-AKT-PTGS2 and EGFR-RAS-RAF-MEK-ERK pathways, and PIK3CA and HRAS are hub genes for adjuvant treatment of BC.

Topics: Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Cyclooxygenase 2; ErbB Receptors; Female; Glucosides; Humans; MicroRNAs; Phenylpropionates; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; raf Kinases; ras Proteins; Signal Transduction

Syringin (Syr), a phenylpropanoid glycoside extracted from Eleutherococcus senticosus, possesses various biological properties, including anticancer activities. However, the cytotoxicity effects of Syr on breast cancer have not yet been elucidated.. In this study, we evaluated the anticancer potential of Syr on breast carcinoma and the mechanism involved.. Non-tumorigenic (M10), tumorigenic (MCF7) and metastatic (MDA-MB-231) breast cancer cell lines as well as xenograft model were treated with Syr. Proliferation and cell cycle distribution were evaluated using the MTT, the colony formation assay and flow cytometry. The expression levels of cytotoxicity-related proteins were detected by Western blot.. Here, we found that colony formation inhibition, cell cycle arrest in the G2/M phase, down-regulation of X-linked inhibitor of apoptosis protein (XIAP), cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3/9 activation were observed in MCF7 and MDA-MB-231 cells treated with Syr. Moreover, pretreatment with a pan-caspase inhibitor (Z-DEVD-FMK) inhibited Syr-induced apoptosis. In addition, treatment with Syr also increased the production of reactive oxygen species (ROS). However, the antioxidant N-acetyl-cysteine (NAC) reversed the ROS levels and rescued the apoptotic changes. Meanwhile, Syr inhibited the growth of breast cancer xenograft models and dramatically decreased tumor volume without any obvious body weight loss in vivo.. Our findings suggest that Syr induces oxidative stress to suppress the proliferation of breast cancer and thus might be an effective therapeutic agent to treat breast cancer.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Caspases; Cell Cycle Checkpoints; Cell Line, Tumor; Female; Glucosides; Humans; MCF-7 Cells; Mice, Inbred BALB C; Oxidative Stress; Phenylpropionates; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Xenograft Model Antitumor Assays