ZnO Q-Dots-Induced Apoptosis Was Coupled with the Induction of PPARγ in Acute Promyelocytic Leukemia Cells; Proposing a Novel Application of Nanoparticles in Combination with Pioglitazone

By the creation of nanoscale-materials, nanotechnology has emerged as one of the focal points of modern medical investigations and nanotechnology-based cancer treatment approaches found their ways into therapeutic strategies. Herein, we evaluated anticancer property and molecular mechanisms of zinc oxide quantum dot nanoparticles (ZnO QD NPs) in the form of nanofluid (NF) in acute promyelocytic leukemia (APL)-derived NB4 cells. ZnO nanofluid (ZnO NF) robustly decreased proliferation of NB4 cells through p21-mediated G1 cell cycle arrest and induced apoptosis probably via ROS-dependent upregulation of FoxO3a and SIRT1. Moreover, our study indicated for the first time that the anti-leukemic effect of ZnO NF was coupled with the up-regulation of peroxisome proliferator-activated receptors gamma (PPAR gamma) in NB4 cells. Activation of PPAR gamma using pioglitazone, not only up-regulated the effect the ZnO NF on the expression of anti-apoptotic target genes but also could significantly elevate the expression of pro-apoptotic molecules in NB4 cells, as compared to either agent alone. In conclusion, this study suggested promising anti-leukemic activity of ZnO NF against NB4 cells and proposed a novel mechanism of action through which ZnO NF may induce significant cytotoxicity in APL, either as a single or in combination with PPAR gamma agonist.

Automated summary

ZnO NF exhibits promising anti-leukemic activity by inhibiting proliferation and inducing apoptosis in NB4 cells through multiple pathways, including G1 cell cycle arrest and upregulation of PPAR gamma. Additionally, combination therapy with PPAR gamma agonist pioglitazone enhances the cytotoxic effect of ZnO NF by modulating the expression of apoptotic genes.