Department of Biomedical Science, CHA University, Kangnak-ku, Seoul, South Korea.
Cell Prolif. 2012 Oct;45(5):420-9. doi: 10.1111/j.1365-2184.2012.00839.x.
The balance between survival and death is a key point for regulation of physiology of stem cells. Recently, applications of natural products to enhance efficiencies in culturing and differentiation of stem cells are increasing. Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) has been known to be toxic to some cancer cells, but it is still unclear whether VCA has a cytotoxic or indeed a proliferative effect on mesenchymal stem cells (MSCs). Here, we have compared effects of VCA in naïve placenta-derived stem cells (PDSCs), immortalized PDSCs and cancer cells (HepG2), and analysed their mechanisms.
MTT assay was performed to analyse effects of VCA on naïve PDSCs, immortalized PDSCs and HepG2. FACS, ROS, caspase-3 assay, western blotting and immunofluorescence were performed to detect signalling events involved in self-renewal of the above cell types.
VCA had cancer cell-specific toxicity to HepG2 cells even with low concentrations of VCA (1-5 pg/ml), toxicity was observed to immortalized PDSCs and HepG2s, while proliferation of naïve PDSCs was significantly increased (P < 0.05). ROS production by VCA treatment in naïve PDSCs was significantly lower compared to controls (P < 0.05). Furthermore, autophagy was activated in naïve PDSCs treated with VCA through increase in type II LC3 and decrease in phosphorylated mTOR.
VCA can promote MSC proliferation through an activated autophagic mechanism.
生存与死亡的平衡是调节干细胞生理学的关键点。最近，应用天然产物来提高干细胞培养和分化效率的应用越来越多。韩国槲寄生凝集素（Viscum album L. var. coloratum agglutinin，VCA）已被证明对某些癌细胞有毒，但尚不清楚 VCA 对间充质干细胞（MSCs）是否具有细胞毒性或增殖作用。在这里，我们比较了 VCA 对原始胎盘来源的干细胞（PDSCs）、永生化 PDSCs 和癌细胞（HepG2）的作用，并分析了它们的机制。
MTT 法分析 VCA 对原始 PDSCs、永生化 PDSCs 和 HepG2 的作用。通过流式细胞术、ROS、caspase-3 测定、western blot 和免疫荧光检测参与上述细胞类型自我更新的信号事件。
VCA 对 HepG2 细胞具有癌细胞特异性毒性，即使 VCA 浓度较低（1-5 pg/ml），也观察到对永生化 PDSCs 和 HepG2s 的毒性，而原始 PDSCs 的增殖显著增加（P <0.05）。VCA 处理后，原始 PDSCs 中的 ROS 产生明显低于对照组（P <0.05）。此外，VCA 处理通过增加 II 型 LC3 和减少磷酸化 mTOR 激活了原始 PDSCs 中的自噬。
VCA 可以通过激活自噬机制促进 MSC 增殖。
