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Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells

Necrosis, apoptosis and autophagic cell death are the main cell death pathways in multicellular organisms, all with distinct and overlapping cellular and biochemical features. DNA damage may trigger different types of cell death in cancer cells but the molecular events governing the mode of cell dea...

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Autores principales: Kutuk, Ozgur, Aytan, Nurgul, Karakas, Bahriye, Kurt, Asli Giray, Acikbas, Ufuk, Temel, Sehime Gulsun, Basaga, Huveyda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552129/
https://www.ncbi.nlm.nih.gov/pubmed/28796811
http://dx.doi.org/10.1371/journal.pone.0182809
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author Kutuk, Ozgur
Aytan, Nurgul
Karakas, Bahriye
Kurt, Asli Giray
Acikbas, Ufuk
Temel, Sehime Gulsun
Basaga, Huveyda
author_facet Kutuk, Ozgur
Aytan, Nurgul
Karakas, Bahriye
Kurt, Asli Giray
Acikbas, Ufuk
Temel, Sehime Gulsun
Basaga, Huveyda
author_sort Kutuk, Ozgur
collection PubMed
description Necrosis, apoptosis and autophagic cell death are the main cell death pathways in multicellular organisms, all with distinct and overlapping cellular and biochemical features. DNA damage may trigger different types of cell death in cancer cells but the molecular events governing the mode of cell death remain elusive. Here we showed that increased BH3-only protein BIK levels promoted cisplatin- and UV-induced mitochondrial apoptosis and biphasic ROS production in HCT-116 wild-type cells. Nonetheless, early single peak of ROS formation along with lysosomal membrane permeabilization and cathepsin activation regulated cisplatin- and UV-induced necrosis in p53-null HCT-116 cells. Of note, necrotic cell death in p53-null HCT-116 cells did not depend on BIK, mitochondrial outer membrane permeabilization or caspase activation. These data demonstrate how cancer cells with different p53 background respond to DNA-damaging agents by integrating distinct cell signaling pathways dictating the mode of cell death.
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spelling pubmed-55521292017-08-25 Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells Kutuk, Ozgur Aytan, Nurgul Karakas, Bahriye Kurt, Asli Giray Acikbas, Ufuk Temel, Sehime Gulsun Basaga, Huveyda PLoS One Research Article Necrosis, apoptosis and autophagic cell death are the main cell death pathways in multicellular organisms, all with distinct and overlapping cellular and biochemical features. DNA damage may trigger different types of cell death in cancer cells but the molecular events governing the mode of cell death remain elusive. Here we showed that increased BH3-only protein BIK levels promoted cisplatin- and UV-induced mitochondrial apoptosis and biphasic ROS production in HCT-116 wild-type cells. Nonetheless, early single peak of ROS formation along with lysosomal membrane permeabilization and cathepsin activation regulated cisplatin- and UV-induced necrosis in p53-null HCT-116 cells. Of note, necrotic cell death in p53-null HCT-116 cells did not depend on BIK, mitochondrial outer membrane permeabilization or caspase activation. These data demonstrate how cancer cells with different p53 background respond to DNA-damaging agents by integrating distinct cell signaling pathways dictating the mode of cell death. Public Library of Science 2017-08-10 /pmc/articles/PMC5552129/ /pubmed/28796811 http://dx.doi.org/10.1371/journal.pone.0182809 Text en © 2017 Kutuk et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kutuk, Ozgur
Aytan, Nurgul
Karakas, Bahriye
Kurt, Asli Giray
Acikbas, Ufuk
Temel, Sehime Gulsun
Basaga, Huveyda
Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells
title Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells
title_full Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells
title_fullStr Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells
title_full_unstemmed Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells
title_short Biphasic ROS production, p53 and BIK dictate the mode of cell death in response to DNA damage in colon cancer cells
title_sort biphasic ros production, p53 and bik dictate the mode of cell death in response to dna damage in colon cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552129/
https://www.ncbi.nlm.nih.gov/pubmed/28796811
http://dx.doi.org/10.1371/journal.pone.0182809
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