Figure 6.

The role of ROS and ATM on Sub-A-mediated mitotic catastrophe. Antioxidant agents inhibited (a) Sub-A-mediated ROS generation, (b) ATM activation and ATF3 upregulation, and (c) mitotic catastrophe. (d) The effect of ATM shRNA transfection on the expression of ATM. Inhibition of ATM decreased the (e) phosphorylation of p53 and (f) mitotic catastrophe. For (a) to (c), cells were pretreated with EUK8 (50 mmol/L) for 1 h, then 30 μM Sub-A was added and incubated for specific times (1 h for ATM activity and 24 h for mitotic catastrophe). For (d) to (f), cells were transfected control or ATM shRNA and then incubated with 30 μM Sub-A for specific times (3 h for p53 phosphorylation and 24 h for mitotic catastrophe). The induction of mitotic catastrophe was determined by counting multinuclear giant cells after DAPI staining. Each value was the mean ± SD of three determinations. The asterisk indicated a significant difference between Sub-A-treated cells and the controls (P < 0.05, by ANOVA with Student's t-test post hoc).