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The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis

Canine mammary tumours (CMTs) are the most common cancer in intact female dogs. In addition to surgery, additional targeted and non-targeted therapies may offer survival benefits to these patients. Therefore, exploring new treatments for CMT is a promising area in veterinary oncology. CMT cells have...

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Autores principales: Cacciola, Nunzio Antonio, Sepe, Fabrizia, Fioriniello, Salvatore, Petillo, Orsolina, Margarucci, Sabrina, Scivicco, Marcello, Peluso, Gianfranco, Balestrieri, Anna, Bifulco, Giovanna, Restucci, Brunella, Severino, Lorella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383333/
https://www.ncbi.nlm.nih.gov/pubmed/37513899
http://dx.doi.org/10.3390/ph16070987
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author Cacciola, Nunzio Antonio
Sepe, Fabrizia
Fioriniello, Salvatore
Petillo, Orsolina
Margarucci, Sabrina
Scivicco, Marcello
Peluso, Gianfranco
Balestrieri, Anna
Bifulco, Giovanna
Restucci, Brunella
Severino, Lorella
author_facet Cacciola, Nunzio Antonio
Sepe, Fabrizia
Fioriniello, Salvatore
Petillo, Orsolina
Margarucci, Sabrina
Scivicco, Marcello
Peluso, Gianfranco
Balestrieri, Anna
Bifulco, Giovanna
Restucci, Brunella
Severino, Lorella
author_sort Cacciola, Nunzio Antonio
collection PubMed
description Canine mammary tumours (CMTs) are the most common cancer in intact female dogs. In addition to surgery, additional targeted and non-targeted therapies may offer survival benefits to these patients. Therefore, exploring new treatments for CMT is a promising area in veterinary oncology. CMT cells have an altered lipid metabolism and use the oxidation of fatty acids for their energy needs. Here we investigated the tumoricidal effects of teglicar, a reversible inhibitor of carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme for fatty acid import into mitochondria, on two CMT cells, P114 and CMT-U229. Viability and apoptosis were examined in CMT cells using the crystal violet assay, trypan blue assay, and flow cytometry analysis. The expression of mediators of apoptosis signalling (e.g., caspase-9, caspase-8, and caspase-3) was assessed by quantitative real-time polymerase chain reaction and western blot analyses. Teglicar was able to decrease cell viability and induce apoptosis in P114 and CMT-U229 cells. At the molecular level, the effect of teglicar was associated with an upregulation of the mRNA expression levels of caspase-9, caspase-8, and caspase-3 and an increase in their protein levels. In summary, our results show that teglicar has a potential effect against CMTs through the induction of apoptotic cell death, making it a promising therapeutic agent against CMTs.
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spelling pubmed-103833332023-07-30 The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis Cacciola, Nunzio Antonio Sepe, Fabrizia Fioriniello, Salvatore Petillo, Orsolina Margarucci, Sabrina Scivicco, Marcello Peluso, Gianfranco Balestrieri, Anna Bifulco, Giovanna Restucci, Brunella Severino, Lorella Pharmaceuticals (Basel) Article Canine mammary tumours (CMTs) are the most common cancer in intact female dogs. In addition to surgery, additional targeted and non-targeted therapies may offer survival benefits to these patients. Therefore, exploring new treatments for CMT is a promising area in veterinary oncology. CMT cells have an altered lipid metabolism and use the oxidation of fatty acids for their energy needs. Here we investigated the tumoricidal effects of teglicar, a reversible inhibitor of carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme for fatty acid import into mitochondria, on two CMT cells, P114 and CMT-U229. Viability and apoptosis were examined in CMT cells using the crystal violet assay, trypan blue assay, and flow cytometry analysis. The expression of mediators of apoptosis signalling (e.g., caspase-9, caspase-8, and caspase-3) was assessed by quantitative real-time polymerase chain reaction and western blot analyses. Teglicar was able to decrease cell viability and induce apoptosis in P114 and CMT-U229 cells. At the molecular level, the effect of teglicar was associated with an upregulation of the mRNA expression levels of caspase-9, caspase-8, and caspase-3 and an increase in their protein levels. In summary, our results show that teglicar has a potential effect against CMTs through the induction of apoptotic cell death, making it a promising therapeutic agent against CMTs. MDPI 2023-07-10 /pmc/articles/PMC10383333/ /pubmed/37513899 http://dx.doi.org/10.3390/ph16070987 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
Cacciola, Nunzio Antonio
Sepe, Fabrizia
Fioriniello, Salvatore
Petillo, Orsolina
Margarucci, Sabrina
Scivicco, Marcello
Peluso, Gianfranco
Balestrieri, Anna
Bifulco, Giovanna
Restucci, Brunella
Severino, Lorella
The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis
title The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis
title_full The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis
title_fullStr The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis
title_full_unstemmed The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis
title_short The Carnitine Palmitoyltransferase 1A Inhibitor Teglicar Shows Promising Antitumour Activity against Canine Mammary Cancer Cells by Inducing Apoptosis
title_sort carnitine palmitoyltransferase 1a inhibitor teglicar shows promising antitumour activity against canine mammary cancer cells by inducing apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383333/
https://www.ncbi.nlm.nih.gov/pubmed/37513899
http://dx.doi.org/10.3390/ph16070987
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