Effect of interaction of magnetic nanoparticles of Fe3O4 and artesunate on apoptosis of K562 cells

Abstract

Ying Wang1, Yuxiang Han1, Yingying Yang1, Jingci Yang1, Xiaonan Guo1, Jingnan Zhang1, Ling Pan1, Guohua Xia2, Baoan Chen21Department of Hematology, the 2nd Hospital of Hebei Medical University, People’s Republic of China; 2Department of Hematology, the Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of ChinaAbstract: The present study evaluated whether the magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) could enhance the activity of artesunate (ART), and to explore its potential mechanisms. Cytotoxicity of the copolymer of ART with MNPs-Fe3O4 on K562 cells was detected by MTT assay and the apoptosis rate of K562 cells was measured by flow cytometry. Protein expression levels of bcl-2, bax, bcl-rambo, caspase-3, and survivin in K562 cells were measured by Western blot. After being incubated with the copolymer of ART with MNPs-Fe3O4 for 48 hours, the growth inhibition rate of K562 cells was significantly increased compared with that of K562 cells treated with ART alone (P < 0.05), and the apoptosis rate of K562 cells was increased significantly compared with that of K562 cells treated with ART alone, suggesting that MNPs-Fe3O4 can enhance the activity of ART. Interestingly, the copolymer-induced cell death was attenuated by caspase inhibitor Z-VAD-FMK. Our results also showed that treatment with the copolymer of MNPs-Fe3O4 and ART increased the expression of bcl-2, bax, bcl-rambo, and caspase-3 proteins, and decreased the expression of survivin protein in K562 cells compared with ART treatment alone. These results suggest that MNPs-Fe3O4 can enhance ART-induced apoptosis, which may be related to the upregulation of bcl-rambo and downregulation of survivin.Keywords: magnetic nanoparticles, MNPs-Fe3O4, artesunate, K562 cells, apoptosis, bcl-rambo