冷等离子体和等离子体处理溶液（PTS）由于其对肿瘤的选择性作用而被认为是癌症治疗的有希望的方法。虽然氧化应激对其效果至关重要，但明确的机制，包括化学介质，仍然不清楚。我们先前报道过空气等离子体活化介质（APAM）表现出肿瘤选择性的抗癌活性。线粒体的断裂和它们围绕受损细胞核的周边区域的不对称组装，也就是单极核周线粒体聚集（MPMC）进一步对其具有作用。随后，我们发现APAM中除了过氧化氢（H2O2）、亚硝酸盐（NO2-）和硝酸盐（NO3-）之外，还有相当数量的臭氧（O3）。在本研究中，我们调查了O3在抗癌效应中的可能作用。为此，我们制备了无氮氧的臭氧化介质ODM。ODM对各种癌细胞具有强烈的细胞毒性，但对非恶性细胞则无影响。ODM还增加了癌细胞中的MPMC、羟基自由基、脂质过氧化物以及它们向核周位点的移动。过氧化氢酶和铁螯合剂可以阻止这些事件和细胞毒性。ODM还降低了细胞内易变铁而增加了线粒体内的易变铁。ODM含有大量的H2O2，但这种氧化剂无法引起MPMC和细胞毒性。这些结果表明，ODM可以模拟APAM的效应，包括MPMC和肿瘤选择性的抗癌效应。这些发现提示，O3在通过引发由H2O2和铁引起的氧化细胞死亡中起着关键作用。版权所有 © 2023 The Authors. 由 Elsevier GmbH 发布.。保留所有权利。

Cold atmospheric plasmas and plasma-treated solutions (PTSs) have emerged as promising approaches in cancer treatment because of their tumor-selective actions. While oxidative stress is critical for their effects, the precise mechanisms, including chemical mediators, remain obscure. Previously, we reported that air plasma-activated medium (APAM) exhibited tumor-selective anticancer activity. The fragmentation of mitochondria and their asymmetrical assembly around the peripheral regions of the damaged nucleus, namely, monopolar perinuclear mitochondrial clustering (MPMC), proceed to the effect. Subsequently, we found that APAM had a substantial amount of O3 in addition to hydrogen peroxide (H2O2), nitrile (NO2-), and nitrate (NO3-). In the present study, we investigated the possible role of O3 in the anticancer effect. For this purpose, we created a nitrogen oxide-free ozonated medium ODM. ODM exhibited potent cytotoxicity against various cancer but not nonmalignant cells. ODM also increased MPMC, hydroxyl radicals, lipid peroxides, and their shifts to perinuclear sites in cancer cells. Catalase and iron chelation prevented these events and cytotoxicity. ODM also decreases the intracellular labile irons while increasing those within mitochondria. ODM had substantial H2O2, but this oxidant failed to cause MPMC and cytotoxicity. These results show that ODM can mimic the effects of APAM, including MPMC and tumor-selective anticancer effects. The findings suggest that O3 is critical in mediating the anticancer effects of APAM by triggering oxidative cell death caused by H2O2 and iron.Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.