ArticleChemical research in toxicology2013
Role of nitric oxide in the chemistry and anticancer activity of etoposide (VP-16,213).
Article in Chemical research in toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Role of Redox Environment in Tumors.Current medicinal chemistry · 2025Review
- Spin Trapping of Nitric Oxide by Hemoglobin and Ferrous Diethyldithiocarbamate in Model Tumors Differing in Vascularization.International journal of molecular sciences · 2024Article
- Review
- Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer.Nature communications · 2021Article
- Role of Oxygen and Nitrogen Radicals in the Mechanism of Anticancer Drug Cytotoxicity.Journal of cancer science & therapy · 2020Article
- Reversal of drug resistance by JS-K and nitric oxide in ABCB1- and ABCG2-expressing multi-drug resistant human tumor cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2019Article
- Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non-Hodgkin lymphoma.Cancer medicine · 2019Article
- Polydopamine Modified Superparamagnetic Iron Oxide Nanoparticles as Multifunctional Nanocarrier for Targeted Prostate Cancer Treatment.Nanomaterials (Basel, Switzerland) · 2019Article
- Nitric oxide reverses drug resistance by inhibiting ATPase activity of p-glycoprotein in human multi-drug resistant cancer cells.Biochimica et biophysica acta. General subjects · 2018Article
- Nitric oxide inhibits ATPase activity and induces resistance to topoisomerase II-poisons in human MCF-7 breast tumor cells.Biochemistry and biophysics reports · 2017Article
- Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells.Biochimica et biophysica acta · 2016Article
- Nitric oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective.Journal of cancer science & therapy · 2016Article
- Nitric Oxide Down-Regulates Topoisomerase I and Induces Camptothecin Resistance in Human Breast MCF-7 Tumor Cells.PloS one · 2015Article
- Effect of nitric oxide on the anticancer activity of the topoisomerase-active drugs etoposide and adriamycin in human melanoma cells.The Journal of pharmacology and experimental therapeutics · 2013Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Originally identified as an innate cytotoxin, nitric oxide ((·)NO) formation in tumors can influence chemotherapy and exacerbate cancer progression. Here, we examined the hypothesis that (·)NO generation contributes to cancer cell drug resistance toward the widely used anticancer drug Etoposide (VP-16). The UV-vis spectrum of VP-16 was not changed by exposure of VP-16 to (·)NO in aqueous buffer. In contrast, reddish-orange compound(s) characteristic of o-quinone- and nitroso-VP-16 were readily generated in a hydrophobic medium (chloroform) in an oxygen-dependent manner. Similar products were also formed when the VP-16 radical, generated from VP-16 and horseradish peroxidase/H2O2, was exposed directly to (·)NO in chloroform in the presence of oxygen. Separation and spectral analysis of VP-16 reaction extracts by electron spin resonance and UV-vis indicated the generation of the phenoxy radical and the o-quinone of VP-16, as well as putative nitroxide, iminoxyl, and other nitrogen oxide intermediates. Nitric oxide products of VP-16 displayed significantly diminished topoisomerase II-dependent cleavage of DNA and cytotoxicity to human HL-60 leukemia cells. LPS-mediated induction of nitric oxide synthase in murine macrophages resulted in VP-16 resistance compared to Raw cells. Furthermore, (·)NO products derived from iNOS rapidly reacted with VP-16 leading to decreased DNA damage and cytotoxicity. Together, these observations suggest that the formation of (·)NO in tumors (associated macrophages) can contribute to VP-16 resistance via the detoxification of VP-16.
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