The effect of curcumin on the differentiation, apoptosis and cell cycle of neural stem cells is mediated through inhibiting autophagy by the modulation of Atg7 and p62

Curcumin is an orange-yellow colored, lipophilic polyphenol substance derived from the rhizome of Curcuma longa that is widely used in many countries. Curcumin has many reported functions, including antioxidant and anti-inflammatory effects. Autophagy removes damaged organelles and protein aggregates in the cell. However, whether curcumin mediates its effects on neural stem cell (NSC) differentiation, cell cycle and apoptosis through autophagy is unknown. In the present study, the effects of curcumin and 3-methyladenine (3MA; an autophagy inhibitor, as a positive control) on the autophagy, differentiation, cell cycle progression and apoptosis of NSCs in different culture states were examined. In order to confirm the role of autophagy in these processes of NSC behavioral change, the protein expression level changes of markers of autophagy, such as autophagy-related protein 7 (Atg7), light chain (LC)3 and p62, were assessed. When NSCs were in an adherent state, 10 µM curcumin inhibited their differentiation into GFAP(+) astrocytes or DCX(+) immature neurons, while Atg7 and p62 protein expression were also reduced compared with the untreated control group. When NSCs were in a suspended state, 10 µM curcumin inhibited the cell cycle progression and apoptosis of NSCs as determined by western blotting, which was associated with a decreased autophagic flux and Atg7 expression. In addition, the curcumin-treated group trended in a similar direction to the 3MA-treated group. Thus, the data suggest that curcumin can inhibit differentiation, promote cell survival and inhibit cell cycle progression from G(1) to S in NSCs, and that these effects are mediated through the regulation of Atg7 and p62.