ArticleRedox biology2013
Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance.
Article in Redox biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- JS-K induces ferroptosis in renal carcinoma cells by regulating the c-Myc-GSTP1 Axis.Scientific reports · 2025Article
- Development of a human colorectal carcinoma cell-based platform for studying inducible nitric oxide synthase expression and nitric oxide signaling dynamics.Frontiers in molecular biosciences · 2025Article
- Click chemistry and drug delivery: A bird's-eye view.Acta pharmaceutica Sinica. B · 2023Review
- Utilizing Estra-1,3,5,16-Tetraene Scaffold: Design and Synthesis of Nitric Oxide Donors as Chemotherapeutic Resistance Combating Agents in Liver Cancer.Molecules (Basel, Switzerland) · 2023Article
- Fifty Years of Diazeniumdiolate Research: A Tribute to Dr. Larry K. Keefer.Critical reviews in oncogenesis · 2023Article
- Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition.Pharmaceuticals (Basel, Switzerland) · 2022Article
- BNTA alleviates inflammatory osteolysis by the SOD mediated anti-oxidation and anti-inflammation effect on inhibiting osteoclastogenesis.Frontiers in pharmacology · 2022Article
- Antimicrobial activity and biocompatibility of the mixture of mineral trioxide aggregate and nitric oxide-releasing compound.Journal of dental sciences · 2021Article
- Differences in the Hemolytic Behavior of Two Isomers inOxidative medicine and cellular longevity · 2020Article
- PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer.Redox biology · 2020Article
- A review of the relatively complex mechanism of JS-K induced apoptosis in cancer cells.Translational cancer research · 2019Review
- Anticancer Activity of Dinitrosyl Iron Complex (NO Donor) on the Multiple Myeloma Cells.Doklady. Biochemistry and biophysics · 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
- The dichotomous role of HBiochemical pharmacology · 2018Review
- Kolaviron was protective against sodium azide (NaN3) induced oxidative stress in the prefrontal cortex.Metabolic brain disease · 2016Article
- G Protein-coupled Receptor 40 (GPR40) and Peroxisome Proliferator-activated Receptor γ (PPARγ): AN INTEGRATED TWO-RECEPTOR SIGNALING PATHWAY.The Journal of biological chemistry · 2015Article
- Nitric oxide is a positive regulator of the Warburg effect in ovarian cancer cells.Cell death & disease · 2014Article
- 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
- Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells.Leukemia research · 2014Article
- Gamma-glutamyl transpeptidase: redox regulation and drug resistance.Advances in cancer research · 2014Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
JS-K is a nitric oxide (NO)-releasing prodrug of the O (2)-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH) via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion) spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.
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Registered trials
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.