XN4 inhibits proliferation of AML cells by inducing oxidative DNA damage / 中国药理学通报

ABSTRACT

Aim To investigate the cytotoxicity of XN4 against AML cells, and the underlying mechanisms by which XN4 might induce DNA damage and apoptotic cell death through reactive oxygen species ( ROS ) . Methods The proliferation inhibition ratio of AML cells was measured by MTT. The level of extracellular ROS, DNA damage, cell cycle process and apoptosis were tested by flow cytometry ( FCM ) . Western blot was applied to test the expression of proteins. Results XN4 significantly inhibited the proliferation of HL-60 and KG1α with IC50 ( 2. 79 ± 0. 15 ) μmol · L-1 and (2. 76 ± 0. 20) μmol·L-1 respectively. XN4 signifi-cantly increased the generation of intracellular ROS, followed by inducing DNA damage and activating the ATM-γ-H2AX signaling, which led to increases of cells in the S phases of the cell cycle. Subsequently, XN4 induced apoptotic cell death through activation of caspase-3 and Parp. Moreover, the above effects were all reversed by the ROS scavenger N-acetylcysteine ( NAC ) . Conclusion XN4-induced DNA damage and cell apoptosis in AML cells are mediated via ROS generation.