Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
PLoS One. 2013 Aug 5;8(8):e69534. doi: 10.1371/journal.pone.0069534. Print 2013.
Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2-50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level.
氧化铜纳米粒子（CuO NPs）在半导体器件、气体传感器、电池、太阳能转换器、微电子和热传递流体中得到了广泛的应用。据报道，纳米粒子通过任何可能的途径进入体内后，肝脏是其靶向器官之一。最近的研究表明，CuO NPs 在肝细胞中具有细胞毒性反应。然而，由于 CuO NPs 暴露导致肝细胞凋亡的潜在机制在很大程度上尚不清楚。我们探索了 CuO NPs 诱导人肝癌 HepG2 细胞凋亡的可能机制。制备的 CuO NPs 呈球形，表面光滑，平均直径为 22nm。研究发现，CuO NPs（浓度范围为 2-50μg/ml）以剂量依赖的方式诱导 HepG2 细胞毒性，这可能是通过活性氧生成和氧化应激介导的。肿瘤抑制基因 p53 和凋亡基因 caspase-3 因 CuO NPs 的暴露而上调。线粒体膜电位的下降伴随着 bax/bcl2 比值的基因表达增加，提示线粒体介导的途径参与了 CuO NPs 诱导的细胞凋亡。本研究为 CuO NPs 在体外引起细胞凋亡的可能机制提供了有价值的见解。应在体内水平进一步研究 CuO NPs 暴露引起细胞凋亡的潜在机制。
