4.6 Article

Anticancer potential of nitric oxide (NO) in neuroblastoma treatment

Journal

RSC ADVANCES
Volume 11, Issue 16, Pages 9112-9120

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1ra00275a

Keywords

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Funding

  1. Colorado State University Chemistry Department
  2. NIH [R01CA31534]
  3. Cancer Prevention Research Institute of Texas (CPRIT) [RP100612, RP120348]
  4. Marie Betzner Morrow Centennial Endowment

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The study found that nitric oxide delivered via S-nitrosoglutathione can exert anti-tumor effects in neuroblastoma, resulting in decreased metabolic activity, reduced clonogenic activity, and lower cell counts and increased dead cell numbers.
The most common extracranial solid tumor in childhood, paediatric neuroblastoma, is frequently diagnosed at advanced stages and identified as high risk. High risk neuroblastoma is aggressive and unpredictable, resulting in poor prognosis and only similar to 40% five-year survival rates. Herein, nitric oxide (NO) delivered via the S-nitrosothiol, S-nitrosoglutathione (GSNO), is explored as an anticancer therapeutic in various neuroblastoma lines. After 24 h of treatment with GSNO, cell viability assays, as assessed by resazurin and MTT ((3-4,5-dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide), consistently identified a moderate, similar to 13-29%, decrease in metabolic activity, colony formation assays revealed notably significant reduction of clonogenic activity, and cytotoxicity assays revealed a visibly significant reduction of total number of cells and live cells as well as an increase in number of dead cells in treated cells versus untreated cells. Thrillingly, RNA-sequence analysis provided highly valuable information regarding the differentially expressed genes in treated samples versus control samples as well as insight into the mechanism of action of NO as an anticancer therapeutic. Favorably, the collective results from these analyses exhibited tumoricidal, non-tumour promoting, and discriminatory characteristics, illuminating the feasibility and significance of NO as a cytotoxic adjuvant in neuroblastoma treatment.

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