K orean mistletoe lectin regulates self‐renewal of placenta‐derived mesenchymal stem cells via autophagic mechanisms

Objectives 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. K orean mistletoe lectin ( V iscum 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 ( MSC s). Here, we have compared effects of VCA in naïve placenta‐derived stem cells ( PDSC s), immortalized PDSC s and cancer cells (HepG2), and analysed their mechanisms. Materials and methods MTT assay was performed to analyse effects of VCA on naïve PDSC s, immortalized PDSC s 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. Results VCA had cancer cell‐specific toxicity to HepG2 cells even with low concentrations of VCA (1–5 pg/ml), toxicity was observed to immortalized PDSC s and HepG2s, while proliferation of naïve PDSC s was significantly increased ( P < 0.05). ROS production by VCA treatment in naïve PDSC s was significantly lower compared to controls ( P < 0.05). Furthermore, autophagy was activated in naïve PDSC s treated with VCA through increase in type II LC 3 and decrease in phosphorylated m TOR . Conclusions VCA can promote MSC proliferation through an activated autophagic mechanism.