ArticleFree radical biology & medicine2007
NQO1-activated phenothiazinium redox cyclers for the targeted bioreductive induction of cancer cell apoptosis.
Article in Free radical biology & medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 63 citations in OpenAlex.
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Review
- Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization, Multiplex RNA Hybridization, Sequencing and Subtyping.International journal of molecular sciences · 2022Article
- The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment.Cancers · 2022Review
- Fluorescent redox-dependent labeling of lipid droplets in cultured cells by reduced phenazine methosulfate.Heliyon · 2020Article
- Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications.Diagnostics (Basel, Switzerland) · 2020Review
- Article
- Understanding of ROS-Inducing Strategy in Anticancer Therapy.Oxidative medicine and cellular longevity · 2019Review
- Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress.Neuroscience · 2015Article
- The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.The Journal of biological chemistry · 2015Article
- In vivo pump-probe optical coherence tomography imaging in Xenopus laevis.Journal of biophotonics · 2015Article
- Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance.The Journal of antimicrobial chemotherapy · 2015Article
- Convenient microtiter plate-based, oxygen-independent activity assays for flavin-dependent oxidoreductases based on different redox dyes.Biotechnology journal · 2014Article
- Phenotypic identification of the redox dye methylene blue as an antagonist of heat shock response gene expression in metastatic melanoma cells.International journal of molecular sciences · 2013Article
- D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis.Apoptosis : an international journal on programmed cell death · 2012Article
- The redox antimalarial dihydroartemisinin targets human metastatic melanoma cells but not primary melanocytes with induction of NOXA-dependent apoptosis.Investigational new drugs · 2012Article
- Discovery of antimicrobial ribonucleotide reductase inhibitors by screening in microwell format.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Thiostrepton is an inducer of oxidative and proteotoxic stress that impairs viability of human melanoma cells but not primary melanocytes.Biochemical pharmacology · 2012Article
- Antimicrobial mechanisms behind photodynamic effect in the presence of hydrogen peroxide.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2011Article
- DCPIP (2,6-dichlorophenolindophenol) as a genotype-directed redox chemotherapeutic targeting NQO1*2 breast carcinoma.Free radical research · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Altered redox signaling and regulation in cancer cells represent a chemical vulnerability that can be targeted by selective chemotherapeutic intervention. Here, we demonstrate that 3,7-diaminophenothiazinium-based redox cyclers (PRC) induce selective cancer cell apoptosis by NAD(P)H:quinone oxidoreductase (NQO1)-dependent bioreductive generation of cellular oxidative stress. Using PRC lead compounds including toluidine blue against human metastatic G361 melanoma cells, apoptosis occurred with phosphatidylserine externalization, loss of mitochondrial transmembrane potential, cytochrome c release, caspase-3 activation, and massive ROS production. Consistent with reductive activation and subsequent redox cycling as the mechanism of PRC cytotoxicity, coincubation with catalase achieved cell protection, whereas reductive antioxidants enhanced PRC cytotoxicity. Unexpectedly, human A375 melanoma cells were resistant to PRC-induced apoptosis, and PRC-sensitive G361 cells were protected by preincubation with the NQO1 inhibitor dicoumarol. Indeed, NQO1 specific enzymatic activity was 9-fold higher in G361 than in A375 cells. The critical role of NQO1 in PRC bioactivation and cytotoxicity was confirmed, when NQO1-transfected breast cancer cells (MCF7-DT15) stably overexpressing active NQO1 displayed strongly enhanced PRC sensitivity as compared to vector control-transfected cells with baseline NQO1 activity. Based on the known overexpression of NQO1 in various tumors these findings suggest the feasibility of developing PRC lead compounds into tumor-selective bioreductive chemotherapeutics.
Indexed as
Identifiers
What OpenQuestion holds
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.