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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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2023-01-01
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| Series: | Advanced Pharmaceutical Bulletin |
| Subjects: | |
| Online Access: | https://apb.tbzmed.ac.ir/PDF/apb-13-176.pdf |
| _version_ | 1827806595390636032 |
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| author | Morteza Golbashirzadeh Hamid Reza Heidari Mehdi Talebi Ahmad Yari Khosroushahi |
| author_facet | Morteza Golbashirzadeh Hamid Reza Heidari Mehdi Talebi Ahmad Yari Khosroushahi |
| author_sort | Morteza Golbashirzadeh |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T21:44:18Z |
| format | Article |
| id | doaj.art-1fa5e78a19da4feba3200718c4a21f6d |
| institution | Directory Open Access Journal |
| issn | 2228-5881 2251-7308 |
| language | English |
| last_indexed | 2024-03-11T21:44:18Z |
| publishDate | 2023-01-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Advanced Pharmaceutical Bulletin |
| spelling | doaj.art-1fa5e78a19da4feba3200718c4a21f6d2023-09-26T10:13:35ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082023-01-0113117618710.34172/apb.2023.019apb-32343Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell LineMorteza Golbashirzadeh0Hamid Reza Heidari1Mehdi Talebi2Ahmad Yari Khosroushahi3Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Hematology and Oncology Research Center, Department of Applied Cell Sciences, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.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.https://apb.tbzmed.ac.ir/PDF/apb-13-176.pdfdrug resistancecisplatinapoptosisferroptosisgene silencing |
| spellingShingle | Morteza Golbashirzadeh Hamid Reza Heidari Mehdi Talebi Ahmad Yari Khosroushahi Ferroptosis as a Potential Cell Death Mechanism Against Cisplatin-Resistant Lung Cancer Cell Line Advanced Pharmaceutical Bulletin drug resistance cisplatin apoptosis ferroptosis gene silencing |
| 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 | drug resistance cisplatin apoptosis ferroptosis gene silencing |
| url | https://apb.tbzmed.ac.ir/PDF/apb-13-176.pdf |
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