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Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines

Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio/chemotherapy are the main approaches used in GC treatment, and there is an urgent need to explore and discover innovative and effective drugs to better...

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Autores principales: Ribeiro, Eduarda, Araújo, Diana, Pereira, Mariana, Lopes, Bruna, Sousa, Patrícia, Sousa, Ana Catarina, Coelho, André, Rêma, Alexandra, Alvites, Rui, Faria, Fátima, Oliveira, Cláudia, Porto, Beatriz, Maurício, Ana Colette, Amorim, Irina, Vale, Nuno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044866/
https://www.ncbi.nlm.nih.gov/pubmed/36979779
http://dx.doi.org/10.3390/biomedicines11030799
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author Ribeiro, Eduarda
Araújo, Diana
Pereira, Mariana
Lopes, Bruna
Sousa, Patrícia
Sousa, Ana Catarina
Coelho, André
Rêma, Alexandra
Alvites, Rui
Faria, Fátima
Oliveira, Cláudia
Porto, Beatriz
Maurício, Ana Colette
Amorim, Irina
Vale, Nuno
author_facet Ribeiro, Eduarda
Araújo, Diana
Pereira, Mariana
Lopes, Bruna
Sousa, Patrícia
Sousa, Ana Catarina
Coelho, André
Rêma, Alexandra
Alvites, Rui
Faria, Fátima
Oliveira, Cláudia
Porto, Beatriz
Maurício, Ana Colette
Amorim, Irina
Vale, Nuno
author_sort Ribeiro, Eduarda
collection PubMed
description Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio/chemotherapy are the main approaches used in GC treatment, and there is an urgent need to explore and discover innovative and effective drugs to better treat this disease. A new strategy arises with the use of repurposed drugs. Drug repurposing coupled with drug combination schemes has been gaining interest in the scientific community. The main objective of this project was to evaluate the therapeutic effects of alternative drugs in GC. For that, three GC cell lines (AGS, MKN28, and MKN45) were used and characterized. Cell viability assays were performed with the reference drug 5-fluororacil (5-FU) and three repurposed drugs: natamycin, nitazoxanide, and benztropine. Nitazoxanide displayed the best results, being active in all GC cells. Further, 5-FU and nitazoxanide in combination were tested in MKN28 GC cells, and the results obtained showed that nitazoxanide alone was the most promising drug for GC therapy. This work demonstrated that the repurposing of drugs as single agents has the ability to decrease GC cell viability in a concentration-dependent manner.
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spelling pubmed-100448662023-03-29 Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines Ribeiro, Eduarda Araújo, Diana Pereira, Mariana Lopes, Bruna Sousa, Patrícia Sousa, Ana Catarina Coelho, André Rêma, Alexandra Alvites, Rui Faria, Fátima Oliveira, Cláudia Porto, Beatriz Maurício, Ana Colette Amorim, Irina Vale, Nuno Biomedicines Article Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio/chemotherapy are the main approaches used in GC treatment, and there is an urgent need to explore and discover innovative and effective drugs to better treat this disease. A new strategy arises with the use of repurposed drugs. Drug repurposing coupled with drug combination schemes has been gaining interest in the scientific community. The main objective of this project was to evaluate the therapeutic effects of alternative drugs in GC. For that, three GC cell lines (AGS, MKN28, and MKN45) were used and characterized. Cell viability assays were performed with the reference drug 5-fluororacil (5-FU) and three repurposed drugs: natamycin, nitazoxanide, and benztropine. Nitazoxanide displayed the best results, being active in all GC cells. Further, 5-FU and nitazoxanide in combination were tested in MKN28 GC cells, and the results obtained showed that nitazoxanide alone was the most promising drug for GC therapy. This work demonstrated that the repurposing of drugs as single agents has the ability to decrease GC cell viability in a concentration-dependent manner. MDPI 2023-03-06 /pmc/articles/PMC10044866/ /pubmed/36979779 http://dx.doi.org/10.3390/biomedicines11030799 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ribeiro, Eduarda
Araújo, Diana
Pereira, Mariana
Lopes, Bruna
Sousa, Patrícia
Sousa, Ana Catarina
Coelho, André
Rêma, Alexandra
Alvites, Rui
Faria, Fátima
Oliveira, Cláudia
Porto, Beatriz
Maurício, Ana Colette
Amorim, Irina
Vale, Nuno
Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_full Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_fullStr Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_full_unstemmed Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_short Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines
title_sort repurposing benztropine, natamycin, and nitazoxanide using drug combination and characterization of gastric cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044866/
https://www.ncbi.nlm.nih.gov/pubmed/36979779
http://dx.doi.org/10.3390/biomedicines11030799
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