ArticleCancer medicine2017
Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma.
Article in Cancer medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Tolcapone Treatment for Cognitive and Behavioral Symptoms in Behavioral Variant Frontotemporal Dementia: A Placebo-Controlled Crossover Study.Journal of Alzheimer's disease : JAD · 2020Trial
- The Seminal Role of the Proinflammatory Cytokine IL-1β and Its Signaling Cascade in Glioblastoma Pathogenesis and the Therapeutic Effect of Interleukin-1β Receptor Antagonist (IL-1RA) and Tolcapone.International journal of molecular sciences · 2025Article
- Article
- Targeting Catechol-O-Methyltransferase Induces Mitochondrial Dysfunction and Enhances the Efficacy of Radiotherapy in Glioma.Cancer research · 2024Article
- 3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.International journal of molecular sciences · 2023Article
- Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone as Potential Therapeutics for Colorectal Cancers.Frontiers in bioinformatics · 2021Article
- Association of high-risk neuroblastoma classification based on expression profiles with differentiation and metabolism.PloS one · 2021Article
- Engineering the TGFβ Receptor to Enhance the Therapeutic Potential of Natural Killer Cells as an Immunotherapy for Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Systems pharmacogenomics - gene, disease, drug and placebo interactions: a case study in COMT.Pharmacogenomics · 2019Article
- Endothelial Colony-Forming Cell Function Is Reduced During HIV Infection.The Journal of infectious diseases · 2019Article
- Endometriosis Malignant Transformation: Epigenetics as a Probable Mechanism in Ovarian Tumorigenesis.International journal of genomics · 2018Review
- Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma.Cancer medicine · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis. Tolcapone also increased ROS while simultaneously decreasing ATP-per-cell in NB cells. Additionally, COMT was inhibited by siRNA in NB cells and showed similar increases in apoptotic markers compared to Tolcapone. In vivo xenograft models displayed inhibition of tumor growth and a significant decrease in time-to-event in mice treated with Tolcapone compared to untreated mice. These results indicate that Tolcapone is cytotoxic to neuroblastoma cells and invite further studies into Tolcapone as a promising novel therapy for the treatment of neuroblastoma.
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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.