ArticleOncotarget2017
Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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.
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Who cites it
51 citing papers in PubMed, 88 citations in OpenAlex.
- Repurposing Antipsychotic Agents in Oncology: Mechanistic Rationale, Emerging Evidence, and Therapeutic Potential.Cancers · 2026Review
- NADPH Dehydrogenase Gene Regulates Energy Distribution and Fatty Acid Metabolism During Fruiting Body Formation in the Filamentous Fungus Podospora anserina.Microbial biotechnology · 2026Article
- Chlorpromazine activates cGAS-STING signaling and reprograms the immune response in glioblastoma.Frontiers in immunology · 2026Article
- A Comprehensive Analysis of the Therapeutic Potential of N-substituted Phenothiazine Derivatives in Medicinal Chemistry.Mini reviews in medicinal chemistry · 2026Review
- Review
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chlorpromazine overcomes temozolomide resistance in glioblastoma by inhibiting Cx43 and essential DNA repair pathways.Journal of translational medicine · 2024Article
- Iloperidone and Temozolomide Synergistically Inhibit Growth, Migration and Enhance Apoptosis in Glioblastoma Cells.Biomedicines · 2024Article
- Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine.International journal of molecular sciences · 2024Article
- Effect of mitochondrial quantity and quality controls in white adipose tissue on healthy lifespan: Essential roles of GH/IGF-1-independent pathways in caloric restriction-mediated metabolic remodeling.Pathology international · 2023Review
- The Role of Dopamine in Repurposing Drugs for Oncology.Biomedicines · 2023Review
- Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma.Antioxidants (Basel, Switzerland) · 2023Article
- Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylatedFrontiers in oncology · 2023Article
- Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells.Frontiers in oncology · 2023Review
- The anti-cancer efficacy of a novel phenothiazine derivative is independent of dopamine and serotonin receptor inhibition.Frontiers in oncology · 2023Article
- Unlocking therapeutic potential: integration of drug repurposing and immunotherapy for various disease targeting.American journal of translational research · 2023Review
- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- Small molecules targeting endocytic uptake and recycling pathways.Frontiers in cell and developmental biology · 2023Review
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with glioblastoma have one of the lowest overall survival rates among patients with cancer. Standard of care for patients with glioblastoma includes temozolomide and radiation therapy, yet 30% of patients do not respond to these treatments and nearly all glioblastoma tumors become resistant. Chlorpromazine is a United States Food and Drug Administration-approved phenothiazine widely used as a psychotropic in clinical practice. Recently, experimental evidence revealed the anti-proliferative activity of chlorpromazine against colon and brain tumors. Here, we used chemoresistant patient-derived glioma stem cells and chemoresistant human glioma cell lines to investigate the effects of chlorpromazine against chemoresistant glioma. Chlorpromazine selectively and significantly inhibited proliferation in chemoresistant glioma cells and glioma stem cells. Mechanistically, chlorpromazine inhibited cytochrome c oxidase (CcO, complex IV) activity from chemoresistant but not chemosensitive cells, without affecting other mitochondrial complexes. Notably, our previous studies revealed that the switch to chemoresistance in glioma cells is accompanied by a switch from the expression of CcO subunit 4 isoform 2 (COX4-2) to COX4-1. In this study, chlorpromazine induced cell cycle arrest selectively in glioma cells expressing COX4-1, and computer-simulated docking studies indicated that chlorpromazine binds more tightly to CcO expressing COX4-1 than to CcO expressing COX4-2. In orthotopic mouse brain tumor models, chlorpromazine treatment significantly increased the median overall survival of mice harboring chemoresistant tumors. These data indicate that chlorpromazine selectively inhibits the growth and proliferation of chemoresistant glioma cells expressing COX4-1. The feasibility of repositioning chlorpromazine for selectively treating chemoresistant glioma tumors should be further explored.
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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.