Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Biochem Mol Toxicol. 2019 Sep;33(9):e22376. doi: 10.1002/jbt.22376. Epub 2019 Jul 21.
Nickel oxide nanoparticles (NiO-NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO-NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO-NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO-NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non-cancerous mouse skin mitochondria. Our results revealed that NiO-NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO-NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti-MCM drug.
氧化镍纳米颗粒（NiO-NPs）在现代工业领域的众多新应用中得到了广泛应用。然而，NiO-NPs 在细胞和分子水平上对人类黑色素瘤细胞系的毒性影响尚未得到明确阐明。因此，本研究旨在研究 NiO-NPs 对恶性皮肤黑色素瘤（MCM）线粒体的体外细胞毒性潜力。结果表明，与非癌性小鼠皮肤线粒体相比，NiO-NPs 显著增加了来自黑色素瘤小鼠模型的皮肤线粒体中活性氧水平、脂质过氧化、线粒体膜电位，同时降低了琥珀酸脱氢酶活性、谷胱甘肽水平和 ATP 含量。我们的结果表明，NiO-NPs 诱导了上述线粒体中的溶酶体膜破裂。本研究表明，NiO-NPs 可显著诱导 MCM 线粒体的选择性细胞毒性。因此，该化合物可能被认为是进一步进行体内和临床研究以获得新型抗 MCM 药物的有前途的候选物。
