Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experimen...

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Main Authors:	Balvan, Jan, Gumulec, Jaromir, Raudenska, Martina, Krizova, Aneta, Stepka, Petr, Babula, Petr, Kizek, Rene, Adam, Vojtech, Masarik, Michal
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679176/

id	pubmed-4679176
recordtype	oai_dc
spelling	pubmed-46791762015-12-31 Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating Balvan, Jan Gumulec, Jaromir Raudenska, Martina Krizova, Aneta Stepka, Petr Babula, Petr Kizek, Rene Adam, Vojtech Masarik, Michal Research Article Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate. Public Library of Science 2015-12-15 /pmc/articles/PMC4679176/ /pubmed/26671576 http://dx.doi.org/10.1371/journal.pone.0145016 Text en © 2015 Balvan 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Balvan, Jan Gumulec, Jaromir Raudenska, Martina Krizova, Aneta Stepka, Petr Babula, Petr Kizek, Rene Adam, Vojtech Masarik, Michal
spellingShingle	Balvan, Jan Gumulec, Jaromir Raudenska, Martina Krizova, Aneta Stepka, Petr Babula, Petr Kizek, Rene Adam, Vojtech Masarik, Michal Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
author_facet	Balvan, Jan Gumulec, Jaromir Raudenska, Martina Krizova, Aneta Stepka, Petr Babula, Petr Kizek, Rene Adam, Vojtech Masarik, Michal
author_sort	Balvan, Jan
title	Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
title_short	Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
title_full	Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
title_fullStr	Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
title_full_unstemmed	Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
title_sort	oxidative stress resistance in metastatic prostate cancer: renewal by self-eating
description	Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679176/
_version_	1613512968419409920

Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

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