Department of Biology, Missouri State University, 901 S National, Springfield, MO 65897, USA.
Department of Chemistry, Missouri State University, Springfield, MO 65897, USA.
Int J Mol Sci. 2023 Feb 17;24(4):4055. doi: 10.3390/ijms24044055.
Metal oxide nanoparticles (MONPs) are widely used in agriculture and food development but there is little understanding of how MONPs, including ZnO, CuO, TiO, and SnO, impact human health and the environment. Our growth assay revealed that none of these (up to 100 µg/mL) negatively affect viability in the budding yeast, . In contrast, both human thyroid cancer cells (ML-1) and rat medullary thyroid cancer cells (CA77) displayed a significant reduction in cell viability with the treatment of CuO and ZnO. The production of reactive oxygen species (ROS) in these cell lines, when treated with CuO and ZnO, was found to be not significantly altered. However, levels of apoptosis with ZnO and CuO were increased, which led us to conclude that the decreased cell viability is mainly caused by non-ROS-mediated cell death. Consistently, data from our RNAseq studies identified differentially regulated pathways associated with inflammation, Wnt, and cadherin signaling across both cell lines, ML-1, and CA77, after ZnO or CuO MONP treatment. Results from gene studies further support non-ROS-mediated apoptosis being the main factor behind decreased cell viability. Together, these findings provide unique evidence that the apoptosis in response to treatment of CuO and ZnO in these thyroid cancer cells was not mainly due to oxidative stress, but to the alteration of a range of signal cascades that promotes cell death.
金属氧化物纳米颗粒（MONPs）广泛应用于农业和食品开发，但人们对 MONPs（包括 ZnO、CuO、TiO 和 SnO）如何影响人类健康和环境知之甚少。我们的生长测定显示，这些 MONPs（高达 100μg/mL）都不会对出芽酵母的活力产生负面影响。相比之下，人类甲状腺癌细胞（ML-1）和大鼠甲状腺髓样癌细胞（CA77）在接受 CuO 和 ZnO 处理后，细胞活力明显下降。在用 CuO 和 ZnO 处理这些细胞系时，活性氧物种（ROS）的产生并没有明显改变。然而，ZnO 和 CuO 处理后的细胞凋亡水平增加，这使我们得出结论，细胞活力的降低主要是由于非 ROS 介导的细胞死亡。一致地，我们的 RNAseq 研究数据表明，在 ZnO 或 CuO MONP 处理后，两种细胞系 ML-1 和 CA77 中与炎症、Wnt 和钙黏蛋白信号相关的途径都发生了差异调节。基因研究的结果进一步支持非 ROS 介导的细胞凋亡是导致细胞活力降低的主要因素。总之，这些发现提供了独特的证据，表明 CuO 和 ZnO 处理甲状腺癌细胞后发生的细胞凋亡主要不是由于氧化应激，而是由于一系列信号级联的改变，促进了细胞死亡。
