Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
Department of Physiology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Phytomedicine. 2019 Aug;61:152844. doi: 10.1016/j.phymed.2019.152844. Epub 2019 Jan 28.
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.
STUDY DESIGN/METHODS: 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.
从刺五加中提取的苯丙素糖苷丁香苷（Syr）具有多种生物活性，包括抗癌活性。然而，Syr 对乳腺癌的细胞毒性作用尚未阐明。
本研究评估了 Syr 对乳腺癌的抗癌潜力及其相关机制。
研究设计/方法：用 Syr 处理非致瘤性（M10）、致瘤性（MCF7）和转移性（MDA-MB-231）乳腺癌细胞系以及异种移植模型。使用 MTT、集落形成实验和流式细胞术评估增殖和细胞周期分布。通过 Western blot 检测细胞毒性相关蛋白的表达水平。
在这里，我们发现 Syr 处理 MCF7 和 MDA-MB-231 细胞后，集落形成抑制、细胞周期阻滞在 G2/M 期、X 连锁凋亡抑制蛋白（XIAP）下调、裂解多聚（ADP-核糖）聚合酶（PARP）和 caspase-3/9 激活。此外，用泛半胱天冬酶抑制剂（Z-DEVD-FMK）预处理可抑制 Syr 诱导的细胞凋亡。此外，Syr 处理还增加了活性氧（ROS）的产生。然而，抗氧化剂 N-乙酰半胱氨酸（NAC）逆转了 ROS 水平并挽救了凋亡变化。同时，Syr 抑制了乳腺癌异种移植模型的生长，并且在体内没有明显的体重减轻的情况下显著降低了肿瘤体积。
我们的研究结果表明，Syr 通过诱导氧化应激来抑制乳腺癌的增殖，因此可能是治疗乳腺癌的有效治疗剂。
