Publication detail

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

BALVAN, J. GUMULEC, J. RAUDENSKÁ, M. KŘÍŽOVÁ, A. ŠTĚPKA, P. BABULA, P. KIZEK, R. ADAM, V. MASAŘÍK, M.

Original Title

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

Type

journal article in Web of Science

Language

English

Original Abstract

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.

Keywords

Oxidative stress; prostate cancer; holographic microscopy

Authors

BALVAN, J.; GUMULEC, J.; RAUDENSKÁ, M.; KŘÍŽOVÁ, A.; ŠTĚPKA, P.; BABULA, P.; KIZEK, R.; ADAM, V.; MASAŘÍK, M.

RIV year

2015

Released

15. 12. 2015

Publisher

PLOS

ISBN

1932-6203

Periodical

PLOS ONE

Year of study

10

Number

12

State

United States of America

Pages from

1

Pages to

23

Pages count

23

URL

http://europepmc.org/articles/PMC4679176?pdf=render

Full text in the Digital Library

http://hdl.handle.net/11012/63726

BibTex

@article{BUT121090,
  author="Jan {Balvan} and Jaromír {Gumulec} and Martina {Raudenská} and Aneta {Křížová} and Petr {Štěpka} and Petr {Babula} and René {Kizek} and Vojtěch {Adam} and Michal {Masařík}",
  title="Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating",
  journal="PLOS ONE",
  year="2015",
  volume="10",
  number="12",
  pages="1--23",
  doi="10.1371/journal.pone.0145016",
  issn="1932-6203",
  url="http://europepmc.org/articles/PMC4679176?pdf=render"
}