Gordon Jenna L, Reynolds Melissa M, Brown Mark A
Department of Chemistry, Colorado State University, Fort Collins, CO 80521, USA.
Department of Chemistry, School of Biomedical Engineering, Colorado State University, Campus Delivery 1872, Fort Collins, CO 80523, USA.
Vet Sci. 2020 Apr 23;7(2):51. doi: 10.3390/vetsci7020051.
Neuroblastoma, the most common extracranial solid tumor in children, accounts for 15% of all pediatric cancer deaths. Pharmaceutical applications of S-Nitrosylation, which, under normal conditions is involved with a host of epigenetic and embryological development pathways, have exhibited great potential for use as adjuvant therapeutics in the clinical management of cancer. Herein, an evaluation of the impact of nitric oxide (NO) as a potent anticancer agent on murine neuroblastoma cells is presented. Excitingly cell viability, colony formation, and non-carcinogenic cell analysis illustrate the significance and practicality of NO as a cytotoxic anticancer therapeutic. Resazurin, WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt), and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide) assays consistently displayed a moderate, ~20-25% reduction in cell viability after exposure to 1 mM -Nitrosoglutathione (GSNO). A colony formation assay demonstrated that treated cells no longer exhibited colony formation capacity. Identically GSNO-treated Adult Human Dermal Fibroblasts (HDFa) exhibited no decrease in viability, indicating potential discrimination between neoplastic and normal cells. Collectively, our findings indicate a potential application for NO as an adjuvant therapeutic in the clinical management of neuroblastoma.
神经母细胞瘤是儿童最常见的颅外实体瘤，占所有儿童癌症死亡病例的15%。S-亚硝基化的药物应用在正常情况下涉及许多表观遗传和胚胎发育途径，在癌症临床管理中作为辅助治疗药物显示出巨大潜力。本文介绍了对一氧化氮（NO）作为一种强效抗癌剂对小鼠神经母细胞瘤细胞影响的评估。令人兴奋的是，细胞活力、集落形成和非致癌细胞分析说明了NO作为一种细胞毒性抗癌治疗药物的重要性和实用性。刃天青、WST-8（2-(2-甲氧基-4-硝基苯基)-3-(4-硝基苯基)-5-(2,4-二磺酸苯基)-2H-四唑单钠盐）和MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐）检测一致显示，在暴露于1 mM亚硝基谷胱甘肽（GSNO）后，细胞活力适度降低约20-25%。集落形成试验表明，处理后的细胞不再具有集落形成能力。同样，经GSNO处理的成人人类皮肤成纤维细胞（HDFa）活力没有下降，表明肿瘤细胞与正常细胞之间可能存在差异。总体而言，我们的研究结果表明NO在神经母细胞瘤临床管理中作为辅助治疗药物具有潜在应用价值。
