Selenite induces DNA damage and specific mitochondrial degeneration in human bladder cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F16%3A10324540" target="_blank" >RIV/00216208:11150/16:10324540 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.tiv.2015.12.011" target="_blank" >http://dx.doi.org/10.1016/j.tiv.2015.12.011</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tiv.2015.12.011" target="_blank" >10.1016/j.tiv.2015.12.011</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Selenite induces DNA damage and specific mitochondrial degeneration in human bladder cancer cells

Popis výsledku v původním jazyce

We have investigated the cytotoxicity and specific effects of selenite in human bladder cancer cell line RT-112 and its clonogenic variant RT-112 HB. Selenite inhibited cell growth and proliferation in both cell lines. Treated cells developed extensive vacuolization which was dose independent but occurring in differing time frames. Ultrastructure analysis revealed that the observed vacuoles are damaged mitochondria and potentially other sub cellular compartments. Selenite-specific effects on mitochondria were further confirmed by mitochondrial membrane potential analysis, changes in ATP production and generation of superoxide. Simultaneously, selenite induced DNA damage in treated cells with activation of p53, PARP-1 and JNK and suppressed autophagy. Cells ultimately died via a combination of apoptosis, necrosis and a distinct type of cell death featuring "vacuolar shrink age", loss of adherence and absence of secondary necrosis as well as other classical markers of either apoptosis or autophagy. The significant presence of so called necroptosis was also not confirmed as the specific inhibitor necrostatin-1 could not prevent cell death. These results thus confirm the toxicity of selenite in bladder cancer cells while pointing at potentially new mechanism of action of this compound in this model.

Název v anglickém jazyce

Selenite induces DNA damage and specific mitochondrial degeneration in human bladder cancer cells

Popis výsledku anglicky

We have investigated the cytotoxicity and specific effects of selenite in human bladder cancer cell line RT-112 and its clonogenic variant RT-112 HB. Selenite inhibited cell growth and proliferation in both cell lines. Treated cells developed extensive vacuolization which was dose independent but occurring in differing time frames. Ultrastructure analysis revealed that the observed vacuoles are damaged mitochondria and potentially other sub cellular compartments. Selenite-specific effects on mitochondria were further confirmed by mitochondrial membrane potential analysis, changes in ATP production and generation of superoxide. Simultaneously, selenite induced DNA damage in treated cells with activation of p53, PARP-1 and JNK and suppressed autophagy. Cells ultimately died via a combination of apoptosis, necrosis and a distinct type of cell death featuring "vacuolar shrink age", loss of adherence and absence of secondary necrosis as well as other classical markers of either apoptosis or autophagy. The significant presence of so called necroptosis was also not confirmed as the specific inhibitor necrostatin-1 could not prevent cell death. These results thus confirm the toxicity of selenite in bladder cancer cells while pointing at potentially new mechanism of action of this compound in this model.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Toxicology in Vitro

ISSN

0887-2333

e-ISSN

—

Svazek periodika

32

Číslo periodika v rámci svazku

Aprile

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

105-114

Kód UT WoS článku

000372760900012

EID výsledku v databázi Scopus

2-s2.0-84952837134