XN4 inhibits proliferation of AML cells by inducing oxidative DNA damage
10.3969/j.issn.1001-1978.2014.04.009
- VernacularTitle:新型化合物XN4抑制急性粒细胞白血病细胞增殖与其诱导氧化性的DNA损伤的关系
- Author:
Lixian WU
;
Lisen HUANG
;
Xianling CHEN
;
Fang KE
;
Ming ZHENG
;
Jianhua XU
- Publication Type:Journal Article
- Keywords:
AML;
DNA damage;
cell cycle arrest;
cell apoptosis;
ROS;
NAC
- From:
Chinese Pharmacological Bulletin
2014;(4):478-483
- CountryChina
- Language:Chinese
-
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.
