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Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis
Cell death can be broadly characterized as either necrosis or apoptosis, depending on the morphological and biochemical features of the cell itself. We have previously reported that the treatment of mouse mammary carcinoma FM3A cells with the anticancer drug floxuridine (FUdR) induces necrosis in th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461588/ https://www.ncbi.nlm.nih.gov/pubmed/32824286 http://dx.doi.org/10.3390/ijms21165876 |
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author | Sato, Akira Hiramoto, Akiko Kim, Hye-Sook Wataya, Yusuke |
author_facet | Sato, Akira Hiramoto, Akiko Kim, Hye-Sook Wataya, Yusuke |
author_sort | Sato, Akira |
collection | PubMed |
description | Cell death can be broadly characterized as either necrosis or apoptosis, depending on the morphological and biochemical features of the cell itself. We have previously reported that the treatment of mouse mammary carcinoma FM3A cells with the anticancer drug floxuridine (FUdR) induces necrosis in the original clone F28-7 but apoptosis in the variant F28-7-A. We have identified regulators, including heat shock protein 90, lamin-B1, cytokeratin-19, and activating transcription factor 3, of cell death mechanisms by using comprehensive gene and protein expression analyses and a phenotype-screening approach. We also observed that the individual inhibition or knockdown of the identified regulators in F28-7 results in a shift from necrotic to apoptotic morphology. Furthermore, we investigated microRNA (miRNA, miR) expression profiles in sister cell strains F28-7 and F28-7-A using miRNA microarray analyses. We found that several unique miRNAs, miR-351-5p and miR-743a-3p, were expressed at higher levels in F28-7-A than in F28-7. Higher expression of these miRNAs in F28-7 induced by transfecting miR mimics resulted in a switch in the mode of cell death from necrosis to apoptosis. Our findings suggest that the identified cell death regulators may play key roles in the decision of cell death mechanism: necrosis or apoptosis. |
format | Online Article Text |
id | pubmed-7461588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74615882020-09-04 Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis Sato, Akira Hiramoto, Akiko Kim, Hye-Sook Wataya, Yusuke Int J Mol Sci Review Cell death can be broadly characterized as either necrosis or apoptosis, depending on the morphological and biochemical features of the cell itself. We have previously reported that the treatment of mouse mammary carcinoma FM3A cells with the anticancer drug floxuridine (FUdR) induces necrosis in the original clone F28-7 but apoptosis in the variant F28-7-A. We have identified regulators, including heat shock protein 90, lamin-B1, cytokeratin-19, and activating transcription factor 3, of cell death mechanisms by using comprehensive gene and protein expression analyses and a phenotype-screening approach. We also observed that the individual inhibition or knockdown of the identified regulators in F28-7 results in a shift from necrotic to apoptotic morphology. Furthermore, we investigated microRNA (miRNA, miR) expression profiles in sister cell strains F28-7 and F28-7-A using miRNA microarray analyses. We found that several unique miRNAs, miR-351-5p and miR-743a-3p, were expressed at higher levels in F28-7-A than in F28-7. Higher expression of these miRNAs in F28-7 induced by transfecting miR mimics resulted in a switch in the mode of cell death from necrosis to apoptosis. Our findings suggest that the identified cell death regulators may play key roles in the decision of cell death mechanism: necrosis or apoptosis. MDPI 2020-08-16 /pmc/articles/PMC7461588/ /pubmed/32824286 http://dx.doi.org/10.3390/ijms21165876 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Sato, Akira Hiramoto, Akiko Kim, Hye-Sook Wataya, Yusuke Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis |
title | Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis |
title_full | Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis |
title_fullStr | Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis |
title_full_unstemmed | Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis |
title_short | Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis |
title_sort | anticancer strategy targeting cell death regulators: switching the mechanism of anticancer floxuridine-induced cell death from necrosis to apoptosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461588/ https://www.ncbi.nlm.nih.gov/pubmed/32824286 http://dx.doi.org/10.3390/ijms21165876 |
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