Induction of ferroptosis cell death in acute promyelocytic leukemia cell lines (NB4 and HL-60) using hydrothermally synthesized ZnO NPs in the presence of black cardamom extract

Abstract

This paper reports an effective, one-step, and eco-friendly method for producing ZnO nanoparticles (NPs) via the hydrothermal procedure. In the synthesis procedure, where 1,8-cineole is the dominant component, an optimized concentration of black cardamom extract is utilized as a capping and reducing agent. The decision to use this extract can be justified because it has a quick reducing capacity. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Dynamic Light Scattering (DLS), and Fourier-transform infrared spectroscopy (FT-IR) have all been used to analyze the NPs. Furthermore, healthy cells (PBMCs) and the Acute Promyelocytic Leukemia cell lines (NB4 and HL-60) were treated to varied concentrations of ZnO NPs for 24 and 48 h. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) test was then used to determine the cell viability. Oxidative and ferroptosis markers were evaluated using commercial kits. Gene expression and cell death were measured using qRT-PCR and flow cytometry. Also, the binding energy and van der Waals interactions of ZnO NP-protein complexes were calculated using molecular docking. On leukemic cells, ZnO NPs displayed growth-inhibiting effects in a time and dose-dependent manner. By considerably boosting lipid-ROS, intracellular iron, ACSL4, and p53 while significantly lowering GSH and GPx activity levels, as well as SLC7A11 and GPx4 mRNA, the ZnO NPs accelerated the ferroptotic cell death. On the other hand, ZnO NPs showed no toxicity to healthy cells. So, based on our research, synthesized ZnO NPs can induce ferroptotic cell death in leukemic cells.

Keywords

• ZnO nanostructures
• Hydrothermal method
• Green chemistry
• Anti-leukemic activities
• Ferroptosis