Some new aspects of erastin-induced ferroptosis in cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F25%3A10159321" target="_blank" >RIV/00098892:_____/25:10159321 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/25:73633517

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0009279725002625?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0009279725002625?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2025.111632" target="_blank" >10.1016/j.cbi.2025.111632</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Some new aspects of erastin-induced ferroptosis in cancer cells

Popis výsledku v původním jazyce

Ferroptosis, a form of regulated cell death (RCD) with unique morphological and biochemical features, has potential in cancer treatment. In this study, erastin (ER)-induced ferroptosis was investigated in cancer cell lines A549, Calu1, and K562. A detailed analysis of the Xc–/GSH/GPX4 axis showed that glutathione (GSH) production, unlike GPX4 expression, is an important factor in influencing the sensitivity of tumor cells to ER despite oncogenic KRAS expression. Here we show for the first time that ferroptosis is associated with marked condensation of cell nuclei, a morphological change that was previously associated exclusively with apoptosis. Importantly, this phenomenon was observed in all three cell lines. Further, thiourea (TU), a known scavenger of reactive oxygen species (ROS) had a complex effect on ER induced ferroptosis. While TU significantly potentiated ER cytotoxicity and changed the mode of cell death from ferroptotic to apoptotic in A549 and K562 cells, it had a mild protective effect in Calu1 cells without changing the mode of cell death. In conclusion, the results show that Xc–-dependent GHS production affects the sensitivity of oncogenic RAS-expressing tumor cells to ER treatment. ER-induced ferroptosis is associated with nuclear condensation. Further, we identified TU as a compound that can change the form of cell death from ferroptotic to apoptotic in some cancer cells. The latter two findings suggest a previously uncovered proximity of the regulatory pathways of ferroptosis and apoptosis.

Název v anglickém jazyce

Some new aspects of erastin-induced ferroptosis in cancer cells

Popis výsledku anglicky

Ferroptosis, a form of regulated cell death (RCD) with unique morphological and biochemical features, has potential in cancer treatment. In this study, erastin (ER)-induced ferroptosis was investigated in cancer cell lines A549, Calu1, and K562. A detailed analysis of the Xc–/GSH/GPX4 axis showed that glutathione (GSH) production, unlike GPX4 expression, is an important factor in influencing the sensitivity of tumor cells to ER despite oncogenic KRAS expression. Here we show for the first time that ferroptosis is associated with marked condensation of cell nuclei, a morphological change that was previously associated exclusively with apoptosis. Importantly, this phenomenon was observed in all three cell lines. Further, thiourea (TU), a known scavenger of reactive oxygen species (ROS) had a complex effect on ER induced ferroptosis. While TU significantly potentiated ER cytotoxicity and changed the mode of cell death from ferroptotic to apoptotic in A549 and K562 cells, it had a mild protective effect in Calu1 cells without changing the mode of cell death. In conclusion, the results show that Xc–-dependent GHS production affects the sensitivity of oncogenic RAS-expressing tumor cells to ER treatment. ER-induced ferroptosis is associated with nuclear condensation. Further, we identified TU as a compound that can change the form of cell death from ferroptotic to apoptotic in some cancer cells. The latter two findings suggest a previously uncovered proximity of the regulatory pathways of ferroptosis and apoptosis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Chemico-Biological Interactions

ISSN

0009-2797

e-ISSN

1872-7786

Svazek periodika

419

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

15

Strana od-do

111632

Kód UT WoS článku

001532079600001

EID výsledku v databázi Scopus

2-s2.0-105009934586