研究动态
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用于在健康人成纤维细胞中传递 NO 的光敏钌亚硝酰候选物的细胞毒性和促氧化特性。

Cytotoxic and pro-oxidant profile of a photosensitive ruthenium nitrosyl candidate for NO delivery in healthy human fibroblasts.

发表日期:2024 Sep
作者: Hande Özbaşak, Hani M Elbeheiry, Martin Schulz, Lucia Račková
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

亚硝酰钌 (Ru-NO) 配合物作为局部治疗应用的光敏一氧化氮 (NO) 供体候选者受到关注。 NO 在皮肤稳态中起着至关重要的调节作用,浓度依赖性地影响增殖、凋亡、自噬和氧化还原平衡等过程。在此背景下,我们研究了 HE-10(一种钌基光诱导 NO 供体)在光照和黑暗条件下对 VH10 人包皮成纤维细胞的促氧化和细胞毒性作用。我们还测试了其细胞内和细胞外NO释放功能。我们的研究揭示了 HE-10 具有显着的剂量依赖性细胞毒性作用、细胞内活性氧和氮物种的增加以及皮肤成纤维细胞凋亡的发生。此外,暴露于剂量不断增加的 HE-10 和白光 LED 光下会导致大量细胞事件,包括显着诱导自噬和 G2/M 期细胞周期停滞。矛盾的是,根据 DAF2-DA NO 探针结果,这些效应不仅仅归因于 NO 释放,这表明除了 NO 光解之外的细胞内光化学反应也有助于 HE-10 的生物活性。这项研究表明,HE-10 表现出细胞毒性和潜在的治疗作用,具体取决于浓度和光照。这些发现对于开发针对皮肤病和潜在某些类型皮肤癌的靶向 Ru-NO 复合物治疗至关重要,在这些疾病中,控制 NO 释放可能是有益的。
Ruthenium nitrosyl (Ru-NO) complexes are of interest as photoactive nitric oxide (NO) donor candidates for local therapeutic applications. NO plays a crucial regulatory role in skin homeostasis, concentration-dependently affecting processes like the proliferation, apoptosis, autophagy and redox balance. In this context, we investigated HE-10, a ruthenium-based photoinducible NO donor, for its pro-oxidant and cytotoxic effects under light and dark conditions in VH10 human foreskin fibroblast cells. We also tested its intracellular and extracellular NO-releasing function. Our study reveals a significant dose-dependent cytotoxic effect of HE-10, an increase in intracellular reactive oxygen and nitrogen species, and the occurrence of apoptosis in skin fibroblast cells. Furthermore, exposure to both increasing doses of HE-10 and white LED light led to substantial cellular events, including a significant induction of autophagy and G2/M phase cell cycle arrest. Paradoxically, these effects were not solely attributable to NO release based on DAF2-DA NO probe results, suggesting that intracellular photochemical reactions additional to NO photolysis contribute to HE-10's biological activity. This study shows that HE-10 exhibits both cytotoxic and potential therapeutic effects, depending on concentration and light exposure. These findings are crucial for developing targeted Ru-NO complex treatments for skin diseases and potentially certain types of skin cancer, where controlled NO release could be beneficial.