Application of ZnO/CNT@Fe3 O4 nanocomposite in amplifying the anti-leukemic effect of imatinib: a novel strategy to adjuvant therapy in chronic myeloid leukemia

Biomedical Materials
Amir-Mohammad YousefiDavood Bashash

Abstract

The advent of tyrosine kinase inhibitors (TKI) in the therapeutic protocols of chronic myeloid leukemia (CML) sparked a flame of hope for patients to finally reach to the milestone of the complete remission. However, by the different mutations bypassing the effectiveness of Imatinib, a powerful impetus has emerged to bring more efficient agents into the field of treatment. The results of the present study declared that the companionship of our synthesized ZnO/CNT@Fe3O4 nanocomposite with Imatinib was able to more efficiently decrease the survival of CML-derived K562 cells probably through inducing reactive oxygen species (ROS)-dependent apoptosis. We also found a superior cytotoxicity in the presence of a well-known autophagy inhibitor, indicating that the apoptotic effect of this treatment was probably enhanced through the suppression of autophagy. Investigating the molecular mechanisms involved in the growth-suppressive effect of ZnO/CNT@Fe3O4-plus-Imatinib clarified that the up-regulation of SIRT1 ceased the progression of the cell cycle, foremost by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors. Notably, we reported for the first time that either direct or indirect suppression of c-Myc resulted...Continue Reading

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