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Revealing New Prospects: Antipsychotic Drugs Induces Anti-Tumor Effects Against Gastric Cancer Through Inducing Apoptosis Publisher Pubmed



Amjadi O1 ; Hedayatizadehomran A2 ; Zaboli E3 ; Janbabaei G4 ; Lira SA5 ; Ahangari G6
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  2. 2. Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
  3. 3. Department of Internal Medicine, Gastrointestinal Cancer Research Center, Non-Communicable Diseases, Mazandaran University of Medical Sciences, Sari, Iran
  4. 4. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Immunology Institute, Ichan School of Medicine at Mount Sinai, New York, United States
  6. 6. Neuroimmunopsychooncogenetic Group, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 1497716316, Tehran, Iran

Source: Current Cancer Drug Targets Published:2025


Abstract

Background and Objective: Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC. Methods: The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining. Results: Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells. Conclusion: Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer. © 2025 Bentham Science Publishers.
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