Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage

Abstract

Background: The most prevalent pediatric cancer is acute lymphoblastic leukemia (ALL). It is exceedingly challenging to treat recurrent diseases, and there aren’t many new medications available for children with disease resistance. The size-dependent anticancer effect of zinc oxide nanoparticles (ZnONPs) on T-cell acute lymphoblastic leukemia (T-ALL) cell line MOLT 3 is the central theme of this study. Methods: The leaf and bark extracts of Diospyros montana were subjected to nanoparticle (NPs) synthesis and characterized analytically to acquire ZnONPs. The ZnONPs were characterized using UV-Vis spectra, DLS, XRD, EDX, SEM, and TEM analysis. Then the ZnONPs were separated into two groups having <50 nm and 50-100 nm NPs sizes. In addition, MTT assay, dual staining, autophagy, DNA damage, and oxidative damage measurement were done to find out the anti-cancer effect of the ZnONPs on MOLT 3 cells. Results: The ZnONPs exhibited a size-dependent anticancer effect against MOLT 3 cells. The IC50 of ZnONPs of < 50 nm was found to be ~75 µg/mL while the IC50 of ZnONPs of 50-100 nm size was found to be ~102 µg/mL. Treatment with ZnONPs of <50 nm size decreased mitochondrial membrane potential, more than that with 50-100 nm ZnONPs. On the other hand, autophagy was found to be more prevalent in 50-100 nm treated ZnONPs when compared with < 50 nm size. However, treatment with both sizes of ZnONPs reduced cell proliferation markers such as ki67 positive cells while increasing 8-OHG and HDCF-DA positive cells. Conclusion: The obtained results portrayed that different-sized ZnONPs induce different modes of T-ALL cell death. Small-sized ZnONPs revealed higher efficacy, highlighting the size-dependent property. Further, this finding denotes that ZnONPs could be an effective anticancer agent against dreadful diseases like T-ALL, warranting further investigation.

Keywords

• acute lymphoblastic leukemia
• dna damage
• diospyros montana
• molt3
• oxidative stress
• zinc oxide nanoparticles