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Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells

The induction of senescence/polyploidization and their role in cancer recurrence is still a poorly explored issue. We showed that MDA-MB-231 and MCF-7 breast cancer cells underwent reversible senescence/polyploidization upon pulse treatment with doxorubicin (dox). Subsequently, senescent/polyploid c...

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Autores principales: Bojko, Agnieszka, Staniak, Karolina, Czarnecka-Herok, Joanna, Sunderland, Piotr, Dudkowska, Magdalena, Śliwińska, Małgorzata Alicja, Salmina, Kristine, Sikora, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504443/
https://www.ncbi.nlm.nih.gov/pubmed/32846959
http://dx.doi.org/10.3390/ijms21176084
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author Bojko, Agnieszka
Staniak, Karolina
Czarnecka-Herok, Joanna
Sunderland, Piotr
Dudkowska, Magdalena
Śliwińska, Małgorzata Alicja
Salmina, Kristine
Sikora, Ewa
author_facet Bojko, Agnieszka
Staniak, Karolina
Czarnecka-Herok, Joanna
Sunderland, Piotr
Dudkowska, Magdalena
Śliwińska, Małgorzata Alicja
Salmina, Kristine
Sikora, Ewa
author_sort Bojko, Agnieszka
collection PubMed
description The induction of senescence/polyploidization and their role in cancer recurrence is still a poorly explored issue. We showed that MDA-MB-231 and MCF-7 breast cancer cells underwent reversible senescence/polyploidization upon pulse treatment with doxorubicin (dox). Subsequently, senescent/polyploid cells produced progeny (escapers) that possessed the same amount of DNA as parental cells. In a dox-induced senescence/polyploidization state, the accumulation of autophagy protein markers, such as LC3B II and p62/SQSTM1, was observed. However, the senescent cells were characterized by a very low rate of new autophagosome formation and degradation, estimated by autophagic index. In contrast to senescent cells, escapers had a substantially increased autophagic index and transcription factor EB activation, but a decreased level of an autophagy inhibitor, Rubicon, and autophagic vesicles with non-degraded cargo. These results strongly suggested that autophagy in escapers was improved, especially in MDA-MB-231 cells. The escapers of both cell lines were also susceptible to dox-induced senescence. However, MDA-MB-231 cells which escaped from senescence were characterized by a lower number of γH2AX foci and a different pattern of interleukin synthesis than senescent cells. Thus, our studies showed that breast cancer cells can undergo senescence uncoupled from autophagy status, but autophagic flux resumption may be indispensable in cancer cell escape from senescence/polyploidy.
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spelling pubmed-75044432020-09-24 Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells Bojko, Agnieszka Staniak, Karolina Czarnecka-Herok, Joanna Sunderland, Piotr Dudkowska, Magdalena Śliwińska, Małgorzata Alicja Salmina, Kristine Sikora, Ewa Int J Mol Sci Article The induction of senescence/polyploidization and their role in cancer recurrence is still a poorly explored issue. We showed that MDA-MB-231 and MCF-7 breast cancer cells underwent reversible senescence/polyploidization upon pulse treatment with doxorubicin (dox). Subsequently, senescent/polyploid cells produced progeny (escapers) that possessed the same amount of DNA as parental cells. In a dox-induced senescence/polyploidization state, the accumulation of autophagy protein markers, such as LC3B II and p62/SQSTM1, was observed. However, the senescent cells were characterized by a very low rate of new autophagosome formation and degradation, estimated by autophagic index. In contrast to senescent cells, escapers had a substantially increased autophagic index and transcription factor EB activation, but a decreased level of an autophagy inhibitor, Rubicon, and autophagic vesicles with non-degraded cargo. These results strongly suggested that autophagy in escapers was improved, especially in MDA-MB-231 cells. The escapers of both cell lines were also susceptible to dox-induced senescence. However, MDA-MB-231 cells which escaped from senescence were characterized by a lower number of γH2AX foci and a different pattern of interleukin synthesis than senescent cells. Thus, our studies showed that breast cancer cells can undergo senescence uncoupled from autophagy status, but autophagic flux resumption may be indispensable in cancer cell escape from senescence/polyploidy. MDPI 2020-08-24 /pmc/articles/PMC7504443/ /pubmed/32846959 http://dx.doi.org/10.3390/ijms21176084 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 Article
Bojko, Agnieszka
Staniak, Karolina
Czarnecka-Herok, Joanna
Sunderland, Piotr
Dudkowska, Magdalena
Śliwińska, Małgorzata Alicja
Salmina, Kristine
Sikora, Ewa
Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
title Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
title_full Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
title_fullStr Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
title_full_unstemmed Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
title_short Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
title_sort improved autophagic flux in escapers from doxorubicin-induced senescence/polyploidy of breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504443/
https://www.ncbi.nlm.nih.gov/pubmed/32846959
http://dx.doi.org/10.3390/ijms21176084
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