Figure 9.

Overview of the ZnO NPs induced cell death pathways. ZnO NPs can induce accumulation of autophagosomes and impair lysosomal functions. Moreover, ZnO NPs can utilize autophagy to enhance zinc ions release through promoting the dissolution of ZnO NPs. The released zinc ions, together with the intracellular zinc ions arising from the inflow of the extracellularly released zinc ions (from the extracellular ZnO NPs), collectively target and damage mitochondrion, resulting in the generation of ROS. The ROS then inhibits cell proliferation by S phase arrest and induce cell apoptosis through the extrinsic (Fas, caspase-8) and intrinsic (bax, bcl-2, caspase9) pathways, ultimately leading to cell death. Elimination of ROS with NAC can completely reverse the cell viability. Inhibiting the early stage autophagy with 3-MA abolishes the apoptosis while inhibiting the late stage autophagy with CQ inversely promotes the apoptosis. In contrast, suppressing apoptosis with z-vad-fmk fails to rescue cell death but enhances autophagy.