ArticleThe Journal of pharmacology and experimental therapeutics2011
The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: involvement of reactive oxygen species.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 68 citations in OpenAlex.
- JS-K induces autophagy-dependent ferroptosis in bladder cancer: a multimodal mechanistic and translational study.Precision clinical medicine · 2026Article
- From Prognostic Marker to Therapeutic Agent: The Role of Nitric Oxide in Lung Cancer.Journal of clinical medicine · 2025Review
- Fifty Years of Diazeniumdiolate Research: A Tribute to Dr. Larry K. Keefer.Critical reviews in oncogenesis · 2023Article
- Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).Molecular medicine reports · 2022Review
- Review
- 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
- A review of the relatively complex mechanism of JS-K induced apoptosis in cancer cells.Translational cancer research · 2019Review
- JS-K, a nitric oxide donor, induces autophagy as a complementary mechanism inhibiting ovarian cancer.BMC cancer · 2019Article
- JS-K induces reactive oxygen species-dependent anti-cancer effects by targeting mitochondria respiratory chain complexes in gastric cancer.Journal of cellular and molecular medicine · 2019Article
- Toxicity mechanism-based prodrugs: glutathione-dependent bioactivation as a strategy for anticancer prodrug design.Expert opinion on drug discovery · 2018Review
- GlutathioneDrug design, development and therapy · 2018Review
- JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells.Oncology letters · 2017Article
- Peroxiredoxin 1 - an antioxidant enzyme in cancer.Journal of cellular and molecular medicine · 2017Review
- Nitrosothiol-Trapping-Based Proteomic Analysis of S-Nitrosylation in Human Lung Carcinoma Cells.PloS one · 2017Article
- N-(2-Hydroxypropyl)methacrylamide Copolymer-Drug Conjugates for Combination Chemotherapy of Acute Myeloid Leukemia.Macromolecular bioscience · 2016Article
- Nitric oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective.Journal of cancer science & therapy · 2016Article
- Effect of hesperidin on mice bearing Ehrlich solid carcinoma maintained on doxorubicin.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.Scientific reports · 2015Article
- Effect of a Pluronic(®) P123 formulation on the nitric oxide-generating drug JS-K.Pharmaceutical research · 2015Article
- Nitric oxide (NO) releasing poly ADP-ribose polymerase 1 (PARP-1) inhibitors targeted to glutathione S-transferase P1-overexpressing cancer cells.Journal of medicinal chemistry · 2014Article
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Non-small-cell lung cancer is among the most common and deadly forms of human malignancies. Early detection is unusual, and there are no curative therapies in most cases. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Here, we show that O(2)-(2,4-dinitrophenyl)-1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) is a potent cytotoxic agent against a subset of human non-small-cell lung cancer cell lines both in vitro and as xenografts in mice. JS-K treatment led to 75% reduction in the growth of H1703 lung adenocarcinoma cells in vivo. Differences in sensitivity to JS-K in different lung cancer cell lines seem to be related to their endogenous levels of reactive oxygen species (ROS)/reactive nitrogen species (RNS). Other related factors, levels of peroxiredoxin 1 (PRX1) and 8-oxo-deoxyguanosine glycosylase (OGG1), also correlated with drug sensitivity. Treatment of the lung adenocarcinoma cells with JS-K resulted in oxidative/nitrosative stress in cells with high basal levels of ROS/RNS, which, combined with the arylating properties of the compound, was reflected in glutathione depletion and alteration in cellular redox potential, mitochondrial membrane permeabilization, and cytochrome c release. Inactivation of manganese superoxide dismutase by nitration was associated with increased superoxide and significant DNA damage. Apoptosis followed these events. Taken together, the data suggest that diazeniumdiolate-based NO-releasing prodrugs may have application as a personalized therapy for lung cancers characterized by high levels of ROS/RNS. PRX1 and OGG1 proteins, which can be easily measured, could function as biomarkers for identifying tumors sensitive to the therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.