Omolbanin Amjadi, Akbar Hedayatizadeh-Omran, Ehsan Zaboli, Ghasem Janbabaei, Sergio A Lira, Ghasem Ahangari
{"title":"Revealing New Prospects: Antipsychotic Drugs Exert Anti-Tumor Effects against Gastric Cancer through Inducing Apoptosis.","authors":"Omolbanin Amjadi, Akbar Hedayatizadeh-Omran, Ehsan Zaboli, Ghasem Janbabaei, Sergio A Lira, Ghasem Ahangari","doi":"10.2174/0115680096303479240614061136","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current cancer drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680096303479240614061136","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
