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The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line
BACKGROUND: Colorectal cancer is one of the most common cancer and the third leading cause of death worldwide. Increased generation of reactive oxygen species (ROS) is observed in many types of cancer cells. Several studies have reported that an increase in ROS production could affect the expression...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472369/ https://www.ncbi.nlm.nih.gov/pubmed/36100939 http://dx.doi.org/10.1186/s12885-022-10055-y |
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author | Cheraghi, Omid Dabirmanesh, Bahareh Ghazi, Farideh Amanlou, Massoud Atabakhshi-kashi, Mona Fathollahi, Yaghoub Khajeh, Khosro |
author_facet | Cheraghi, Omid Dabirmanesh, Bahareh Ghazi, Farideh Amanlou, Massoud Atabakhshi-kashi, Mona Fathollahi, Yaghoub Khajeh, Khosro |
author_sort | Cheraghi, Omid |
collection | PubMed |
description | BACKGROUND: Colorectal cancer is one of the most common cancer and the third leading cause of death worldwide. Increased generation of reactive oxygen species (ROS) is observed in many types of cancer cells. Several studies have reported that an increase in ROS production could affect the expression of proteins involved in ROS-scavenging, detoxification and drug resistance. Nuclear factor erythroid 2 related factor 2 (Nrf(2)) is a known transcription factor for cellular response to oxidative stress. Several researches exhibited that Nrf(2) could exert multiple functions and expected to be a promising therapeutic target in many cancers. Here, Nrf(2) was knocked down in colorectal cancer cell line HT29 and changes that occurred in signaling pathways and survival mechanisms were evaluated. METHODS: The influence of chemotherapy drugs (doxorubicin and cisplatin), metastasis and cell viability were investigated. To explore the association between specific pathways and viability in HT29-Nrf(2)(−), proteomic analysis, realtime PCR and western blotting were performed. RESULTS: In the absence of Nrf(2) (Nrf(2)(−)), ROS scavenging and detoxification potential were dramatically faded and the HT29-Nrf(2)(−) cells became more susceptible to drugs. However, a severe decrease in viability was not observed. Bioinformatic analysis of proteomic data revealed that in Nrf(2)(−) cells, proteins involved in detoxification processes, respiratory electron transport chain and mitochondrial-related compartment were down regulated. Furthermore, proteins related to MAPKs, JNK and FOXO pathways were up regulated that possibly helped to overcome the detrimental effect of excessive ROS production. CONCLUSIONS: Our results revealed MAPKs, JNK and FOXO pathways connections in reducing the deleterious effect of Nrf(2) deficiency, which can be considered in cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10055-y. |
format | Online Article Text |
id | pubmed-9472369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94723692022-09-15 The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line Cheraghi, Omid Dabirmanesh, Bahareh Ghazi, Farideh Amanlou, Massoud Atabakhshi-kashi, Mona Fathollahi, Yaghoub Khajeh, Khosro BMC Cancer Research BACKGROUND: Colorectal cancer is one of the most common cancer and the third leading cause of death worldwide. Increased generation of reactive oxygen species (ROS) is observed in many types of cancer cells. Several studies have reported that an increase in ROS production could affect the expression of proteins involved in ROS-scavenging, detoxification and drug resistance. Nuclear factor erythroid 2 related factor 2 (Nrf(2)) is a known transcription factor for cellular response to oxidative stress. Several researches exhibited that Nrf(2) could exert multiple functions and expected to be a promising therapeutic target in many cancers. Here, Nrf(2) was knocked down in colorectal cancer cell line HT29 and changes that occurred in signaling pathways and survival mechanisms were evaluated. METHODS: The influence of chemotherapy drugs (doxorubicin and cisplatin), metastasis and cell viability were investigated. To explore the association between specific pathways and viability in HT29-Nrf(2)(−), proteomic analysis, realtime PCR and western blotting were performed. RESULTS: In the absence of Nrf(2) (Nrf(2)(−)), ROS scavenging and detoxification potential were dramatically faded and the HT29-Nrf(2)(−) cells became more susceptible to drugs. However, a severe decrease in viability was not observed. Bioinformatic analysis of proteomic data revealed that in Nrf(2)(−) cells, proteins involved in detoxification processes, respiratory electron transport chain and mitochondrial-related compartment were down regulated. Furthermore, proteins related to MAPKs, JNK and FOXO pathways were up regulated that possibly helped to overcome the detrimental effect of excessive ROS production. CONCLUSIONS: Our results revealed MAPKs, JNK and FOXO pathways connections in reducing the deleterious effect of Nrf(2) deficiency, which can be considered in cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10055-y. BioMed Central 2022-09-13 /pmc/articles/PMC9472369/ /pubmed/36100939 http://dx.doi.org/10.1186/s12885-022-10055-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Cheraghi, Omid Dabirmanesh, Bahareh Ghazi, Farideh Amanlou, Massoud Atabakhshi-kashi, Mona Fathollahi, Yaghoub Khajeh, Khosro The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
title | The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
title_full | The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
title_fullStr | The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
title_full_unstemmed | The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
title_short | The effect of Nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
title_sort | effect of nrf(2) deletion on the proteomic signature in a human colorectal cancer cell line |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472369/ https://www.ncbi.nlm.nih.gov/pubmed/36100939 http://dx.doi.org/10.1186/s12885-022-10055-y |
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