CNP mediated selective toxicity on melanoma cells is accompanied by mitochondrial dysfunction.,PLOS ONE

当前位置： X-MOL 学术 › PLOS ONE › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CNP mediated selective toxicity on melanoma cells is accompanied by mitochondrial dysfunction.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-01-17 , DOI: 10.1371/journal.pone.0227926
Elif Aplak ₁ , Claudia von Montfort ₁ , Lisa Haasler ₁ , David Stucki ₁ , Bodo Steckel ₂ , Andreas S Reichert ₁ , Wilhelm Stahl ₁ , Peter Brenneisen ₁

Affiliation

Cerium (Ce) oxide nanoparticles (CNP; nanoceria) are reported to have cytotoxic effects on certain cancerous cell lines, while at the same concentration they show no cytotoxicity on normal (healthy) cells. Redox-active CNP exhibit both selective prooxidative as well as antioxidative properties. The former is proposed to be responsible for impairment of tumor growth and invasion and the latter for rescuing normal cells from reactive oxygen species (ROS)-induced damage. Here we address possible underlying mechanisms of prooxidative effects of CNP in a metastatic human melanoma cell line. Malignant melanoma is the most aggressive form of skin cancer, and once it becomes metastatic the prognosis is very poor. We have shown earlier that CNP selectively kill A375 melanoma cells by increasing intracellular ROS levels, whose basic amount is significantly higher than in the normal (healthy) counterpart, the melanocytes. Here we show that CNP initiate a mitochondrial increase of ROS levels accompanied by an increase in mitochondrial thiol oxidation. Furthermore, we observed CNP-induced changes in mitochondrial bioenergetics, dynamics, and cristae morphology demonstrating mitochondrial dysfunction which finally led to tumor cell death. CNP-induced cell death is abolished by administration of PEG-conjugated catalase. Overall, we propose that cerium oxide nanoparticles mediate cell death via hydrogen peroxide production linked to mitochondrial dysfunction.

中文翻译：

CNP介导的对黑色素瘤细胞的选择性毒性伴随着线粒体功能障碍。

据报道，氧化铈（Ce）纳米颗粒（CNP; nanoceria）对某些癌细胞系具有细胞毒性作用，而在相同浓度下，它们对正常（健康）细胞没有细胞毒性。具有氧化还原活性的CNP表现出选择性的氧化性和抗氧化性。提议前者负责肿瘤生长和侵袭的损害，而后者负责从活性氧（ROS）诱导的损伤中拯救正常细胞。在这里，我们探讨了转移性人黑素瘤细胞系中CNP促氧化作用的潜在潜在机制。恶性黑色素瘤是皮肤癌最具有侵略性的形式，一旦转移，则预后很差。前面我们已经表明，CNP通过增加细胞内ROS水平选择性地杀死A375黑色素瘤细胞，其基本含量明显高于正常（健康）的黑素细胞。在这里，我们显示CNP启动ROS水平的线粒体增加，并伴随着线粒体硫醇氧化的增加。此外，我们观察到CNP诱导的线粒体生物能学，动力学和cr状形态变化表明线粒体功能障碍，最终导致肿瘤细胞死亡。通过施用PEG缀合的过氧化氢酶，消除了CNP诱导的细胞死亡。总体而言，我们建议氧化铈纳米颗粒通过与线粒体功能障碍相关的过氧化氢产生来介导细胞死亡。我们观察到CNP诱导的线粒体生物能学，动力学和cr形态的变化表明线粒体功能障碍，最终导致肿瘤细胞死亡。通过施用PEG缀合的过氧化氢酶，消除了CNP诱导的细胞死亡。总体而言，我们建议氧化铈纳米颗粒通过与线粒体功能障碍相关的过氧化氢产生来介导细胞死亡。我们观察到CNP诱导的线粒体生物能学，动力学和cr形态的变化表明线粒体功能障碍，最终导致肿瘤细胞死亡。通过施用PEG缀合的过氧化氢酶，消除了CNP诱导的细胞死亡。总体而言，我们建议氧化铈纳米颗粒通过与线粒体功能障碍相关的过氧化氢产生来介导细胞死亡。

更新日期：2020-01-21

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11