ArticleInternational journal of molecular sciences2019
Thioridazine Enhances P62-Mediated Autophagy and Apoptosis Through Wnt/β-Catenin Signaling Pathway in Glioma Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Repurposing Antipsychotic Agents in Oncology: Mechanistic Rationale, Emerging Evidence, and Therapeutic Potential.Cancers · 2026Review
- From Antipsychotic to Antitumor Agent: Cariprazine Suppresses Glioblastoma via D2/D3-ARRB2 Axis Modulation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Synthesis and Cytotoxic Activity Study of Conjugates of N-Acyl Derivatives of 3,5-Bis(benzylidene)-4-piperidones and Phenothiazine.International journal of molecular sciences · 2026Article
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- CPUK02 sensitizes U87 glioblastoma cell lines to TMZ treatment via autophagy flux inhibition.Molecular biology research communications · 2026Article
- Identification and Characterization of Static Craniofacial Defects in Pre-MetamorphicJournal of developmental biology · 2025Article
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Silencing FGL1 promotes prostate cancer cell apoptosis and inhibits EMT progression.Scientific reports · 2025Article
- Circular RNAs inducing the osteogenic differentiation of dental mesenchymal stem cellsWorld journal of stem cells · 2025Review
- Targeting Autophagy as a Strategy for Developing New Host-Directed Therapeutics Against Nontuberculous Mycobacteria.Pathogens (Basel, Switzerland) · 2025Review
- Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.Molecular neurobiology · 2025Review
- Pan-cancer drivers of metastasis.Molecular cancer · 2025Article
- Platycodin D Enhances Glioma Sensitivity to Temozolomide by Inhibition of the Wnt/β-Catenin Pathway.Drug design, development and therapy · 2025Article
- Therapeutic strategies for colorectal cancer: antitumor efficacy of dopamine D2 receptor antagonists.Toxicological research · 2024Review
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy.EMBO molecular medicine · 2024Article
- Revisiting the potential of regulated cell death in glioma treatment: a focus on autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis, immunogenic cell death, and the crosstalk between them.Frontiers in oncology · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/β-catenin signaling. After THD treatment, Fzd-1 and GSK3β-S9 phosphorylation (inactivated form) was reduced to promote β-catenin degradation, which attenuated P62 inhibition. The autophagy marker LC3-II markedly increased when P62 was released from β-catenin inhibition. Additionally, the P62-dependent caspase-8 activation that induced P53-independent apoptosis was confirmed by inhibiting T-cell factor/β-catenin and autophagy flux. Moreover, treatment with THD combined with temozolomide (TMZ) engendered increased LC3-II expression and caspase-3 activity, indicating promising drug synergism. In conclusion, THD induces autophagy in GBM cells by not only upregulating AMPK activity, but also enhancing P62-mediated autophagy and apoptosis through Wnt/β-catenin signaling. Therefore, THD is a potential alternative therapeutic agent for drug repositioning in GBM.
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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.