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

Ying Wang¹, Yuxiang Han¹, Yingying Yang¹, Jingci Yang¹, Xiaonan Guo¹, Jingnan Zhang¹, Ling Pan¹, Guohua Xia², Baoan Chen^2
1Department 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 China

Abstract: 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