ZnO/CNT@Fe3O4 induces ROS-mediated apoptosis in chronic myeloid leukemia (CML) cells: an emerging prospective for nanoparticles in leukemia treatment

Abstract

The advent of nanoparticles revolutionised the drug delivery systems in human diseases; however, their prominent role was highlighted in the cancer-based therapies, where this technology could specifically target cancer cells. Herein, we decided to combine two nanoparticles Fe3O4 and ZnO to fabricate a new anti-cancer nanocomposite. Noteworthy, hydroxylated carbon nanotube (CNT) was used to increase the water-solubility of the compound, improving its uptake by malignant cells. This study was designed to evaluate the anticancer property as well as the molecular mechanisms of ZnO/CNT@Fe3O4 nanocomposite cytotoxicity in CML-derived K562 cells. Our results outlined that ZnO/CNT@Fe3O4 decreased the proliferative capacity of K562 cells through induction of G1 arrest and induced apoptosis probably via ROS-dependent upregulation of FOXO3a and SIRT1. The results of qRT-PCR analysis also demonstrated that while ZnO/CNT@Fe3O4 significantly increased the expression of pro-apoptotic genes in K562 cells, it had no significant inhibitory effect on the expression levels of anti-apoptotic target genes of NF-κB; proposing an attenuating role of NF-κB signalling pathway in K562 cell response to ZnO/CNT@Fe3O4. Synergistic experiment showed that ZnO/CNT@Fe3O4 could enhance the cytotoxic effects of imatinib on K562 cells. Overall, it seems that pharmaceutical application of nanocomposites possesses novel promising potential for leukaemia treatment strategies.

Keywords

• Nanocomposite
• chronic myeloid leukaemia
• NF-κB
• apoptosis