Anticancer potential of nitric oxide (NO) in neuroblastoma treatment

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 ∼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, ∼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.

[1]  E. N. Nolte-‘t Hoen,et al.  Orally Administered 5-aminolevulinic Acid for Isolation and Characterization of Circulating Tumor-Derived Extracellular Vesicles in Glioblastoma Patients , 2020, Cancers.

[2]  Mark A. Brown,et al.  Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells , 2020, Veterinary sciences.

[3]  M. Gaze,et al.  Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1) , 2020, Cancers.

[4]  Joseph G Ibrahim,et al.  Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences , 2018, bioRxiv.

[5]  M. Schoenfisch,et al.  Anticancer potency of nitric oxide-releasing liposomes. , 2017, RSC advances.

[6]  Bryndon J. Oleson,et al.  Dual Role of Nitric Oxide in Regulating the Response of β Cells to DNA Damage. , 2017, Antioxidants & redox signaling.

[7]  Junjie Fu,et al.  Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects. , 2017, Journal of medicinal chemistry.

[8]  Xueqian Wang,et al.  Effects of JS-K, a novel anti-cancer nitric oxide prodrug, on gene expression in human hepatoma Hep3B cells. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[9]  J. Shohet,et al.  Neuroblastoma , 2017, British Medical Journal.

[10]  M. Reynolds,et al.  Correlating S-nitrosothiol decomposition and NO release for modified poly(lactic-co-glycolic acid) polymer films , 2014 .

[11]  D. Chan,et al.  Identification of a natural product-like STAT3 dimerization inhibitor by structure-based virtual screening , 2014, Cell Death and Disease.

[12]  Yan Li,et al.  Allele-specific imbalance of oxidative stress-induced growth inhibitor 1 associates with progression of hepatocellular carcinoma. , 2014, Gastroenterology.

[13]  J. Black,et al.  Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment. , 2014, Bioorganic & medicinal chemistry.

[14]  T. Maeda,et al.  Acidic extracellular microenvironment and cancer , 2013, Cancer Cell International.

[15]  A. Gadbail,et al.  Nitric oxide and cancer: a review , 2013, World Journal of Surgical Oncology.

[16]  R. Lock,et al.  Tumor Protein 53-Induced Nuclear Protein 1 Enhances p53 Function and Represses Tumorigenesis , 2013, Front. Genet..

[17]  Melissa M. Reynolds,et al.  Applications for nitric oxide in halting proliferation of tumor cells. , 2013, Biochemical and biophysical research communications.

[18]  Quanyi Lu,et al.  DNMT3A mutations and clinical features in Chinese patients with acute myeloid leukemia , 2013, Cancer Cell International.

[19]  Hong-tao Lu,et al.  Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in renal cell carcinoma , 2013, World Journal of Surgical Oncology.

[20]  A. Naranjo,et al.  A Prospective Study of Expectant Observation as Primary Therapy for Neuroblastoma in Young Infants: A Children's Oncology Group Study , 2012, Annals of surgery.

[21]  A. Papazoglou,et al.  Growth‐inhibitory and chemosensitizing effects of the glutathione‐S‐transferase‐π‐activated nitric oxide donor PABA/NO in malignant gliomas , 2012, International journal of cancer.

[22]  Chang-Ju Kim,et al.  Protective Effect of Coriolus versicolor Cultivated in Citrus Extract Against Nitric Oxide-Induced Apoptosis in Human Neuroblastoma SK-N-MC Cells , 2011, Experimental neurobiology.

[23]  Jae Ho Shin,et al.  Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth. , 2010, Molecular pharmaceutics.

[24]  V. Rotter,et al.  p53‐dependent transcriptional regulation of EDA2R and its involvement in chemotherapy‐induced hair loss , 2010, FEBS letters.

[25]  Jason R. Hickok,et al.  Nitric oxide and cancer therapy: the emperor has NO clothes. , 2010, Current pharmaceutical design.

[26]  P. Siesjö,et al.  The dual role of nitric oxide in glioma. , 2010, Current pharmaceutical design.

[27]  K. Matthay,et al.  Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  L. Martin,et al.  Adult Motor Neuron Apoptosis Is Mediated by Nitric Oxide and Fas Death Receptor Linked by DNA Damage and p53 Activation , 2005, The Journal of Neuroscience.

[29]  H. Hayashi,et al.  TRB3, a novel ER stress‐inducible gene, is induced via ATF4–CHOP pathway and is involved in cell death , 2005, The EMBO journal.

[30]  D. Townsend,et al.  Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug. , 2004, Molecular pharmacology.

[31]  S. Oyadomari,et al.  Roles of CHOP/GADD153 in endoplasmic reticulum stress , 2004, Cell Death and Differentiation.

[32]  C. Bergeron,et al.  Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy , 2003, British Journal of Cancer.

[33]  P. Montevecchi,et al.  A kinetic study of S-nitrosothiol decomposition. , 2002, Chemistry.

[34]  Kai Chen,et al.  Neurons Overexpressing Heme Oxygenase‐1 Resist Oxidative Stress‐Mediated Cell Death , 2000, Journal of neurochemistry.

[35]  D. Stram,et al.  Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children's Cancer Group study. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  K. Isobe,et al.  Mitogen-activated protein kinase pathway mediates peroxynitrite-induced apoptosis in human dopaminergic neuroblastoma SH-SY5Y cells. , 1999, Biochemical and biophysical research communications.

[37]  D. L. Williams,et al.  The Chemistry of S-Nitrosothiols , 1999 .

[38]  P. Andreana,et al.  Targeting nitric oxide to cancer cells: cytotoxicity studies of glyco-S-nitrosothiols. , 1999, Bioorganic & medicinal chemistry letters.

[39]  James B. Mitchell,et al.  The multifaceted roles of nitric oxide in cancer. , 1998, Carcinogenesis.

[40]  G. Chaudhuri,et al.  Dual Role of Nitric Oxide in Cancer Biology , 2010 .

[41]  B. Bonavida Nitric oxide (NO) and cancer , 2010 .

[42]  Salvador Moncada,et al.  Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway , 2004, Nature Cell Biology.

[43]  D. Stram,et al.  Biologic variables in the outcome of stages I and II neuroblastoma treated with surgery as primary therapy: a children's cancer group study. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.