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Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway

OBJECTIVE: Our research aims to assess the influence of erastin, a ferroptosis-inducing agent, on cervical cancer cells. INTRODUCTION: Cervical cancer is a prevalent malignancy in females. Dysregulation of ferroptosis, a form of cell demise reliant on iron, is implicated in several cancers. METHODS:...

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Detalles Bibliográficos
Autores principales: Wei, Xiaoning, Huang, Qiaoqiao, Huang, Jinbing, Yu, Li, Chen, Junying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687934/
https://www.ncbi.nlm.nih.gov/pubmed/38031977
http://dx.doi.org/10.1177/03946320231219348
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author Wei, Xiaoning
Huang, Qiaoqiao
Huang, Jinbing
Yu, Li
Chen, Junying
author_facet Wei, Xiaoning
Huang, Qiaoqiao
Huang, Jinbing
Yu, Li
Chen, Junying
author_sort Wei, Xiaoning
collection PubMed
description OBJECTIVE: Our research aims to assess the influence of erastin, a ferroptosis-inducing agent, on cervical cancer cells. INTRODUCTION: Cervical cancer is a prevalent malignancy in females. Dysregulation of ferroptosis, a form of cell demise reliant on iron, is implicated in several cancers. METHODS: The effect of erastin on HeLa and SiHa was detected by transwell assay, scratch test, and colony formation assay, while cell apoptosis was detected using flow cytometry. Cellular reactive oxygen species (ROS) generation was detected using the dichloro-dihydro-fluorescein diacetate assay. Sequencing analysis identified differentially expressed genes (DEGs), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment analyses were employed to identify the target gene. Subsequently, the utilization of small interfering RNA (siRNA) was employed to suppress the targeted gene expression in HeLa cells, thereby effectively mitigating the impact of erastin on various cellular processes including invasion, colony formation, migration, and ROS generation. RESULTS: The findings indicate that erastin attenuates the viability of both HeLa cells (IC(50) = 30.88 µM) and SiHa cells (IC(50) = 29.40 µM). Treatment with erastin at 10 µM inhibits the invasion, colony formation, and migration of both HeLa and SiHa cells within 24 h. Ferrostatin-1 (1 µM) notably alleviates the inhibitory effects of erastin of HeLa and SiHa cells. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target, heme oxygenase-1 (HO-1), was found in erastin-treated cells compared to the control group. When knocked down HO-1 in HeLa cells, effectively counteracting the effects of erastin on the invasion, colony formation, migration, and ROS production in HeLa cells. CONCLUSION: Our research demonstrates that erastin induces ferroptosis and the accumulation of ROS in cervical cancer cells by activating the Nrf2/HO-1 pathway, significantly reducing cell proliferation and motility. These findings propose a potential molecular mechanism of erastin-mediated cervical cancer development.
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spelling pubmed-106879342023-11-30 Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway Wei, Xiaoning Huang, Qiaoqiao Huang, Jinbing Yu, Li Chen, Junying Int J Immunopathol Pharmacol Original Research Article OBJECTIVE: Our research aims to assess the influence of erastin, a ferroptosis-inducing agent, on cervical cancer cells. INTRODUCTION: Cervical cancer is a prevalent malignancy in females. Dysregulation of ferroptosis, a form of cell demise reliant on iron, is implicated in several cancers. METHODS: The effect of erastin on HeLa and SiHa was detected by transwell assay, scratch test, and colony formation assay, while cell apoptosis was detected using flow cytometry. Cellular reactive oxygen species (ROS) generation was detected using the dichloro-dihydro-fluorescein diacetate assay. Sequencing analysis identified differentially expressed genes (DEGs), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment analyses were employed to identify the target gene. Subsequently, the utilization of small interfering RNA (siRNA) was employed to suppress the targeted gene expression in HeLa cells, thereby effectively mitigating the impact of erastin on various cellular processes including invasion, colony formation, migration, and ROS generation. RESULTS: The findings indicate that erastin attenuates the viability of both HeLa cells (IC(50) = 30.88 µM) and SiHa cells (IC(50) = 29.40 µM). Treatment with erastin at 10 µM inhibits the invasion, colony formation, and migration of both HeLa and SiHa cells within 24 h. Ferrostatin-1 (1 µM) notably alleviates the inhibitory effects of erastin of HeLa and SiHa cells. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target, heme oxygenase-1 (HO-1), was found in erastin-treated cells compared to the control group. When knocked down HO-1 in HeLa cells, effectively counteracting the effects of erastin on the invasion, colony formation, migration, and ROS production in HeLa cells. CONCLUSION: Our research demonstrates that erastin induces ferroptosis and the accumulation of ROS in cervical cancer cells by activating the Nrf2/HO-1 pathway, significantly reducing cell proliferation and motility. These findings propose a potential molecular mechanism of erastin-mediated cervical cancer development. SAGE Publications 2023-11-30 /pmc/articles/PMC10687934/ /pubmed/38031977 http://dx.doi.org/10.1177/03946320231219348 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Article
Wei, Xiaoning
Huang, Qiaoqiao
Huang, Jinbing
Yu, Li
Chen, Junying
Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway
title Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway
title_full Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway
title_fullStr Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway
title_full_unstemmed Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway
title_short Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway
title_sort erastin induces ferroptosis in cervical cancer cells via nrf2/ho-1 signaling pathway
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687934/
https://www.ncbi.nlm.nih.gov/pubmed/38031977
http://dx.doi.org/10.1177/03946320231219348
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