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Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells

Cisplatin is a potent chemotherapeutic drug for ovarian cancer (OC) treatment. However, its efficacy is significantly limited due to the development of cisplatin resistance. Although the acquisition of cisplatin resistance is a complex process involving various molecular alterations within cancer ce...

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Autor principal: Chun, Jaemoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419319/
https://www.ncbi.nlm.nih.gov/pubmed/37569773
http://dx.doi.org/10.3390/ijms241512397
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author Chun, Jaemoo
author_facet Chun, Jaemoo
author_sort Chun, Jaemoo
collection PubMed
description Cisplatin is a potent chemotherapeutic drug for ovarian cancer (OC) treatment. However, its efficacy is significantly limited due to the development of cisplatin resistance. Although the acquisition of cisplatin resistance is a complex process involving various molecular alterations within cancer cells, the increased reliance of cisplatin-resistant cells on glycolysis has gained increasing attention. Isoalantolactone, a sesquiterpene lactone isolated from Inula helenium L., possesses various pharmacological properties, including anticancer activity. In this study, isoalantolactone was investigated as a potential glycolysis inhibitor to overcome cisplatin resistance in OC. Isoalantolactone effectively targeted key glycolytic enzymes (e.g., lactate dehydrogenase A, phosphofructokinase liver type, and hexokinase 2), reducing glucose consumption and lactate production in cisplatin-resistant OC cells (specifically A2780 and SNU-8). Importantly, it also sensitized these cells to cisplatin-induced apoptosis. Isoalantolactone–cisplatin treatment regulated mitogen-activated protein kinase and AKT pathways more effectively in cisplatin-resistant cells than individual treatments. In vivo studies using cisplatin-sensitive and resistant OC xenograft models revealed that isoalantolactone, either alone or in combination with cisplatin, significantly suppressed tumor growth in cisplatin-resistant tumors. These findings highlight the potential of isoalantolactone as a novel glycolysis inhibitor for treating cisplatin-resistant OC. By targeting the dysregulated glycolytic pathway, isoalantolactone offers a promising approach to overcoming drug resistance and enhancing the efficacy of cisplatin-based therapies.
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spelling pubmed-104193192023-08-12 Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells Chun, Jaemoo Int J Mol Sci Article Cisplatin is a potent chemotherapeutic drug for ovarian cancer (OC) treatment. However, its efficacy is significantly limited due to the development of cisplatin resistance. Although the acquisition of cisplatin resistance is a complex process involving various molecular alterations within cancer cells, the increased reliance of cisplatin-resistant cells on glycolysis has gained increasing attention. Isoalantolactone, a sesquiterpene lactone isolated from Inula helenium L., possesses various pharmacological properties, including anticancer activity. In this study, isoalantolactone was investigated as a potential glycolysis inhibitor to overcome cisplatin resistance in OC. Isoalantolactone effectively targeted key glycolytic enzymes (e.g., lactate dehydrogenase A, phosphofructokinase liver type, and hexokinase 2), reducing glucose consumption and lactate production in cisplatin-resistant OC cells (specifically A2780 and SNU-8). Importantly, it also sensitized these cells to cisplatin-induced apoptosis. Isoalantolactone–cisplatin treatment regulated mitogen-activated protein kinase and AKT pathways more effectively in cisplatin-resistant cells than individual treatments. In vivo studies using cisplatin-sensitive and resistant OC xenograft models revealed that isoalantolactone, either alone or in combination with cisplatin, significantly suppressed tumor growth in cisplatin-resistant tumors. These findings highlight the potential of isoalantolactone as a novel glycolysis inhibitor for treating cisplatin-resistant OC. By targeting the dysregulated glycolytic pathway, isoalantolactone offers a promising approach to overcoming drug resistance and enhancing the efficacy of cisplatin-based therapies. MDPI 2023-08-03 /pmc/articles/PMC10419319/ /pubmed/37569773 http://dx.doi.org/10.3390/ijms241512397 Text en © 2023 by the author. 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
Chun, Jaemoo
Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells
title Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells
title_full Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells
title_fullStr Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells
title_full_unstemmed Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells
title_short Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells
title_sort isoalantolactone suppresses glycolysis and resensitizes cisplatin-based chemotherapy in cisplatin-resistant ovarian cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419319/
https://www.ncbi.nlm.nih.gov/pubmed/37569773
http://dx.doi.org/10.3390/ijms241512397
work_keys_str_mv AT chunjaemoo isoalantolactonesuppressesglycolysisandresensitizescisplatinbasedchemotherapyincisplatinresistantovariancancercells