ArticleCell death & disease2022
Targeting DRD2 by the antipsychotic drug, penfluridol, retards growth of renal cell carcinoma via inducing stemness inhibition and autophagy-mediated apoptosis.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Repurposing Antipsychotics in Cancer Therapy: Modulation of Autophagy Mechanisms.Clinical drug investigation · 2026Review
- Review
- Study of the Mechanism by Which Shenfu Injection Regulates Cardiomyocyte Hypertrophy Based on Dopamine Receptor D2-Mediated Mitochondrial Fission.Anatolian journal of cardiology · 2026Article
- Identification of Paraptosis-Related Renal Cell Carcinoma Subtypes, Construction of a Prognostic Signature, and Determination of Tumor Microenvironment Landscape Using Bioinformatic Analysis and Experimental Verification.Current issues in molecular biology · 2026Article
- Drug repurposing in oncology: a path beyond the bottleneck.Medical oncology (Northwood, London, England) · 2025Review
- Multifaceted roles of OCT4 in tumor microenvironment: biology and therapeutic implications.Oncogene · 2025Review
- Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.Discover oncology · 2025Review
- Neurotransmitter-Mimicking Nanovesicles Facilitate Postoperative Glioblastoma Stem Cell-Specific Treatment for Preventing Tumor Recurrence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Probing the Molecular Mechanisms of Kratom's Antipsychotic Effects through a Multi-modal Computational Approach.Current pharmaceutical design · 2025Article
- Quercetin ameliorates renal injury in hyperuricemic rats via modulating ER stress pathways.Frontiers in pharmacology · 2025Article
- Anti-neoplastic effects of the antipsychotic drug penfluridol in preclinical prostate cancer models.Frontiers in oncology · 2025Article
- Repurposing the antipsychotic drug penfluridol for cancer treatment (Review).Oncology reports · 2024Review
- Multi-objective latent space optimization of generative molecular design models.Patterns (New York, N.Y.) · 2024Article
- Silyl Radicals as Single-Electron Reductants: α-Aminoalkyl Radical Formation via a Photocatalytic Oxidatively Initiated Radical Chain Process.Journal of the American Chemical Society · 2024Article
- Inhalation Anesthetics Play a Janus-Faced Role in Self-Renewal and Differentiation of Stem Cells.Biomolecules · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories.iScience · 2023Article
- Drug Repurposing of Generic Drugs: Challenges and the Potential Role for Government.Applied health economics and health policy · 2023Article
- Dissecting the novel abilities of aripiprazole: The generation of anti-colorectal cancer effects by targeting GActa pharmaceutica Sinica. B · 2023Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies with poor prognoses, since it is largely resistant to chemotherapy, radiotherapy, and targeted therapy. The persistence of cancer stem cells (CSCs) is the major cause of treatment failure with RCC. Recent evidence showed that dopamine receptor D2 (DRD2)-targeting antipsychotic drugs such as penfluridol exert oncostatic effects on several cancer types, but the effect of penfluridol on RCC remains unknown. Here, we uncovered penfluridol suppressed in vitro cell growth and in vivo tumorigenicity of various RCC cell lines (Caki-1, 786-O, A498, and ACHN) and enhanced the Sutent (sunitinib)-triggered growth inhibition on clear cell (cc)RCC cell lines. Mechanistically, upregulation of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) was critical for autophagy-mediated apoptosis induced by penfluridol. Transcriptional inhibition of OCT4 and Nanog via inhibiting GLI1 was important for penfluridol-induced stemness and proliferation inhibition. The anticancer activities of penfluridol on ccRCC partially occurred through DRD2. In clinical ccRCC specimens, positive correlations of DRD2 with GLI1, OCT4, and Nanog were observed and their expressions were correlated with worse prognoses. Summarizing, DRD2 antagonists such as penfluridol induce UPR signaling and suppress the GLI1/OCT4/Nanog axis in ccRCC cells to reduce their growth through inducing autophagy-mediated apoptosis and stemness inhibition. These drugs can be repurposed as potential agents to treat ccRCC patients.
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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 Socratic graph.