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Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line

Purpose: Drug resistance is a challenging issue in cancer chemotherapy. Cell death induction is one of the main strategies to overcome chemotherapy resistance. Notably, ferroptosis has been considered a critical cell death mechanism in recent years. Accordingly, in this study, the different cell dea...

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Autores principales: Golbashirzadeh, Morteza, Heidari, Hamid Reza, Talebi, Mehdi, Yari Khosroushahi, Ahmad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Tabriz University of Medical Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871276/
https://www.ncbi.nlm.nih.gov/pubmed/36721820
http://dx.doi.org/10.34172/apb.2023.019
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author Golbashirzadeh, Morteza
Heidari, Hamid Reza
Talebi, Mehdi
Yari Khosroushahi, Ahmad
author_facet Golbashirzadeh, Morteza
Heidari, Hamid Reza
Talebi, Mehdi
Yari Khosroushahi, Ahmad
author_sort Golbashirzadeh, Morteza
collection PubMed
description Purpose: Drug resistance is a challenging issue in cancer chemotherapy. Cell death induction is one of the main strategies to overcome chemotherapy resistance. Notably, ferroptosis has been considered a critical cell death mechanism in recent years. Accordingly, in this study, the different cell death strategies focused on ferroptosis have been utilized to overcome cisplatin resistance in an in vitro lung cancer model. Methods: The physiological functions of Akt1 and GPX4, as critical targets for ferroptosis and apoptosis induction, were suppressed by siRNA or antagonistic agents in resistant A549 cells. Afterward, the interventions’ impacts on cell viability and reactive oxygen species (ROS) amount were analyzed by flow cytometry. Moreover, the alteration in the relevant gene and protein expression levels were quantified using Real-time PCR and western blot methods. Results: The result showed that the treatment with Akt1 siRNA reversed the cisplatin resistance in the A549 cell line through the induction of apoptosis. Likewise, the combination treatment of the GPX4 siRNA or FIN56 as ferroptosis inducers alongside cisplatin elevated ROS’s cellular level, reduced the cellular antioxidant genes level and increased the cisplatin cytotoxic effect. Conclusion: In conclusion, our study indicated that ferroptosis induction can be considered a promising cell death strategy in cisplatin-resistant cancer cells.
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spelling pubmed-98712762023-01-30 Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line Golbashirzadeh, Morteza Heidari, Hamid Reza Talebi, Mehdi Yari Khosroushahi, Ahmad Adv Pharm Bull Research Article Purpose: Drug resistance is a challenging issue in cancer chemotherapy. Cell death induction is one of the main strategies to overcome chemotherapy resistance. Notably, ferroptosis has been considered a critical cell death mechanism in recent years. Accordingly, in this study, the different cell death strategies focused on ferroptosis have been utilized to overcome cisplatin resistance in an in vitro lung cancer model. Methods: The physiological functions of Akt1 and GPX4, as critical targets for ferroptosis and apoptosis induction, were suppressed by siRNA or antagonistic agents in resistant A549 cells. Afterward, the interventions’ impacts on cell viability and reactive oxygen species (ROS) amount were analyzed by flow cytometry. Moreover, the alteration in the relevant gene and protein expression levels were quantified using Real-time PCR and western blot methods. Results: The result showed that the treatment with Akt1 siRNA reversed the cisplatin resistance in the A549 cell line through the induction of apoptosis. Likewise, the combination treatment of the GPX4 siRNA or FIN56 as ferroptosis inducers alongside cisplatin elevated ROS’s cellular level, reduced the cellular antioxidant genes level and increased the cisplatin cytotoxic effect. Conclusion: In conclusion, our study indicated that ferroptosis induction can be considered a promising cell death strategy in cisplatin-resistant cancer cells. Tabriz University of Medical Sciences 2023-01 2021-11-10 /pmc/articles/PMC9871276/ /pubmed/36721820 http://dx.doi.org/10.34172/apb.2023.019 Text en ©2023 The Authors. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.
spellingShingle Research Article
Golbashirzadeh, Morteza
Heidari, Hamid Reza
Talebi, Mehdi
Yari Khosroushahi, Ahmad
Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line
title Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line
title_full Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line
title_fullStr Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line
title_full_unstemmed Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line
title_short Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line
title_sort ferroptosis as a potential cell death mechanism against cisplatin-resistant lung cancer cell line
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871276/
https://www.ncbi.nlm.nih.gov/pubmed/36721820
http://dx.doi.org/10.34172/apb.2023.019
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