Induction of immunogenic cell death in cancer cells by a photoactivated platinum(iv) prodrug

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00537437" target="_blank" >RIV/68081707:_____/20:00537437 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/20:73603653

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2020/QI/D0QI00991A#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2020/QI/D0QI00991A#!divAbstract</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d0qi00991a" target="_blank" >10.1039/d0qi00991a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Induction of immunogenic cell death in cancer cells by a photoactivated platinum(iv) prodrug

Popis výsledku v původním jazyce

The platinum(iv) prodrug trans,trans,trans-[Pt(N-3)(2)(OH)(2)(py)(2)] (1) is stable and non-toxic in the dark, but potently cytotoxic to cancer cells when irradiated by visible light, including cisplatin-resistant cells. On irradiation with visible light, it generates reactive Pt(ii) species which can attack DNA, and produces reactive oxygen species (ROS) and reactive nitrogen species (RNS) which exert unusual effects on biochemical pathways. We now show that its novel mechanism of action includes induction of immunogenic cell death (ICD). Treatment of cancer cells with 1 followed by photoirradiation with visible light induces calreticulin (CRT) expression at the surface of dying cancer cells. This is accompanied by release of high mobility group protein-1B (HMGB1) and the secretion of ATP. Autophagy appears to play a key role in this chemotherapeutically-stimulated ICD. The observed uneven distribution of ecto-CRT promotes phagocytosis, confirmed by the observation of engulfment of photoirradiated CT26 colorectal cancer cells treated with 1 by J774.A1 macrophages. The photoactivatable prodrug 1 has a unique mechanism of action which distinguishes it from other platinum drugs due to its immunomodulating properties, which may enhance its anticancer efficacy.

Název v anglickém jazyce

Induction of immunogenic cell death in cancer cells by a photoactivated platinum(iv) prodrug

Popis výsledku anglicky

The platinum(iv) prodrug trans,trans,trans-[Pt(N-3)(2)(OH)(2)(py)(2)] (1) is stable and non-toxic in the dark, but potently cytotoxic to cancer cells when irradiated by visible light, including cisplatin-resistant cells. On irradiation with visible light, it generates reactive Pt(ii) species which can attack DNA, and produces reactive oxygen species (ROS) and reactive nitrogen species (RNS) which exert unusual effects on biochemical pathways. We now show that its novel mechanism of action includes induction of immunogenic cell death (ICD). Treatment of cancer cells with 1 followed by photoirradiation with visible light induces calreticulin (CRT) expression at the surface of dying cancer cells. This is accompanied by release of high mobility group protein-1B (HMGB1) and the secretion of ATP. Autophagy appears to play a key role in this chemotherapeutically-stimulated ICD. The observed uneven distribution of ecto-CRT promotes phagocytosis, confirmed by the observation of engulfment of photoirradiated CT26 colorectal cancer cells treated with 1 by J774.A1 macrophages. The photoactivatable prodrug 1 has a unique mechanism of action which distinguishes it from other platinum drugs due to its immunomodulating properties, which may enhance its anticancer efficacy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/GA18-09502S" target="_blank" >GA18-09502S: Ovlivnění rezistence nádorových buněk k chemoterapii s cílem obnovit jejich citlivost k novým, existujícím a dosud neúspěšným metalofarmakům</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

4150-4159

Kód UT WoS článku

000585823500011

EID výsledku v databázi Scopus

2-s2.0-85095133992