TW01001, a novel piperazinedione compound, induces mitotic arrest and autophagy in non-small cell lung cancer A549 cells

• TW01001 induced cells to accumulate at G2/M phase, which ultimately led to cell apoptotic death.
• TW01001 upregulates p53 protein expression and induces p53-independent autophagy.
• TW01001 induces autophagy-p53-signaling pathway to cause mitotic arrest and cell growth inhibition in A549 cells.

Here, we report that TW01001, a novel piperazinedione compound, could be a new mitotic inhibitor for the treatment of non-small cell lung cancer by the following observations in A549 cells: (1) induction of cells to accumulate at G2/M phase, which ultimately led to cell apoptotic death, (2) accumulation of p53 and inhibition of survival signalings, and (3) induction of p53-independent autophagy. Taken together, our data suggested that TW01001 induces autophagy-p53-signaling pathway to cause mitotic arrest and cell growth inhibition in A549 cells and provides the framework for further development as a novel therapeutic agent for lung cancer treatment.