Targeting nitric oxide to cancer cells: cytotoxicity studies of glyco-S-nitrosothiols

Hou, Yongchun; Wang, Jianqiang; Andreana, Peter R.; Cantauria, Guilleherme; Tarasia, Srikumar; Sharp, Laura; Braunschweiger, Paul G.; Wang, Peng George

doi:10.1016/s0960-894x(99)00363-7

Cited by 40 publications

(27 citation statements)

References 25 publications

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“…Although NO concentration can be directly manipulated, it is more challenging to control release kinetics and site-specific delivery of NO. To address these challenges various delivery platforms have been explored [23][24][25][26][27][28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…Various NO-based therapeutics have been utilized in cancer research, including nitrated fatty acids, NO-loaded nanoparticles, and NO-donors [25][26][27][28][29][32][33][34][35][36]40]. NO-donors including diazeniumdiolates and RSNOs have been successfully applied to influence or control NO release kinetics in anticancer research [25][26][27][28][29]32,33,40]. Diazeniumdiolates, which consist of two moles of NO per molecule (vs one mole of NO per RSNO molecule), result in higher concentrations of NO-release than RSNOs.…”

Section: Discussionmentioning

confidence: 99%

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Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Gordon

Reynolds

Brown

2020

Veterinary Sciences

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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 S-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. Vet. Sci. 2020, 7, 51 2 of 15 and intricacy of disease progression and response to treatment, the International Neuroblastoma Staging System (INSS) was developed to classify the extent of the disease and impact the treatment approach [13]. Three distinct stages comprise the INSS: low, intermediate, and high risk. Each risk group is comprised of definitions containing the stage(s), patient age, presence/absence of the MYCN gene, histology, and DNA ploidy. Currently, low risk tumors represent ≤25% of initial diagnoses, intermediate risk represent about~15% of initial diagnoses, and high risk tumors are the most commonly diagnosed, at ≥60% [11]. In patients with low risk disease, surgery and observation are the central therapeutic options that contribute to >90% survival [14,15]. Patients with intermediate risk disease typically receive a variety of sequential treatments including chemotherapy, surgery, and radiation therapy, if necessary. Survival rates in this group drop some but remain favorable at >80% [16,17]. High risk treatment protocols commence in an identical manner and additional treatments are frequently required, such as immunotherapy and bone marrow transplant. Despite the advances in treatments for low and intermediate risk disease, patients with high risk disease continue to face particularly poor prognosis, with~40% five-year overall survival rates [18,19]. Overall relapse rates are additionally overwhelming, at >60% [12]. In a similar fashion, treatments for recurrent low-risk and intermediate-risk disease are largely effective. However, recurrent high-risk neuroblastoma remains a significant challenge. Due to the a...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Gordon

Reynolds

Brown

2020

Veterinary Sciences

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“…The cytotoxicity of glucose-2-SNAP (E.2) and fructose-2-SNAP (E.4) were evaluated and compared against E.1 using DU-145 human prostate cells in vitro. E.2 was found to be 4× more cytotoxic than E.1, while E.4 was found to be 13× more cytotoxic than E.1 (Hou et al 1999a). …”

Section: Nitrosothiols (Rsnos)mentioning

confidence: 84%

Nitric Oxide-Releasing Molecules for Cancer Therapy and Chemoprevention

Anand

Thatcher

2010

Nitric Oxide (NO) and Cancer

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The Nobel Prize for Medicine and Physiology in 1998 to Furchgott, Ignarro, and Murad provided a new impetus to research in prodrugs of the messenger molecule, nitric oxide (NO). Although more famously known for its cardiovascular roles in the treatment of angina (nitrates) and more recently erectile dysfunction (Viagra R ), NO has been extensively researched within the realm of cancer biology. This review briefly highlights the various chemical classes of NO donors with potential utility in cancer chemotherapy and chemoprevention. These molecules release NO upon bioactivation and thus engender the therapeutic rationale of using them in a clinical setting. Bearing these factors in mind, and in the light of current research findings, special emphasis is given to a newer generation of NORMs (nitric oxide-releasing molecules), viz., NONOates, NO-NSAIDs, and furoxans.

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“…The inflammatory process which is involved in wound healing evades the normal wound healing process bysubtle modifications in the cancer milieu. In cancer, the Tregs, MDSCs and TAMs exhibit pro-tumoural functions and participate in suppression of adaptive immunity [2,10,14,27,28,[29][30][31][32]. The immature myeloid cells from the bone marrow that are normally involved in woundhealing exhibit a state of immune suppression during carcinogenesis [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

“…Tumor-associated macrophages exhibit pro-tumoural functions and participate in suppression of adaptive immunity [11]. They also exhibit functional plasticity and also show reversible adaptation to changing environments [16,28].The TAMs, MDSCs, dendritic cells, NK cells, tumor cells, neutrophils, eosinophils, basophils, and endothelial cells have been reported to release NO and free radicals, which influence physiological functions in the tumor microenvironment [10,11,19,21,[29][30][31][32].…”

Section: Free Radical Releasing Cells In Tumor Milieumentioning

confidence: 99%

The Metabolomics of Nitric Oxide and Reactive Nitrogen Species in Immune Editing Tumor Milieu: Influence of Nitric Oxide-Modulating Therapies

Amin¹

2012

J Drug Metab Toxicol

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Targeting nitric oxide to cancer cells: cytotoxicity studies of glyco-S-nitrosothiols

Cited by 40 publications

References 25 publications

Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Nitric Oxide-Releasing Molecules for Cancer Therapy and Chemoprevention

The Metabolomics of Nitric Oxide and Reactive Nitrogen Species in Immune Editing Tumor Milieu: Influence of Nitric Oxide-Modulating Therapies

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