Cell Cycle-Related Induction of Apoptosis of NB4 Cells by Arsenic Trioxide is Associated with Difference in Reactive Oxygen Species Level in Cell Cycle

Objective To explore the association of cell cycle related induction of apoptosis of NB4 cells by arsenic trioxide(As 2O 3) with the level of reactive oxygen species (ROS) in cell cycle. Methods Double staining flow cytometry was performed, using 7-amino actinomycin D and dihydrorhodamin 123 (or alternatively 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate), to display the level fluctuation of reactive oxygen species (ROS) during a normal cell cycle of NB4 cells. Flow cytometry using PI staining was applied to analyze the cell cycle distribution and apoptosis. Results NB4 cells possessed higher level of ROS in G 2/M phase than in G 1 and S phases. As 2O 3 (2μmol/L) induced a predominant apoptosis of NB4 cells from G 2/M phase, and this efficacy was amplified upon coadministration of DMNQ which could produce the endogenous ROS. Conclusion Selective induction of apoptosis of NB4 cells from G 2/M phase is associated with a higher ROS level in this phase. It suggests that the cell cycle_related apoptotic sensitivity to As 2O 3 is related to ROS level of the cells.