Dipyridophenazine iridium(III) complex as a phototoxic cancer stem cell selective, mitochondria targeting agent

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00557968" target="_blank" >RIV/68081707:_____/22:00557968 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0009279722001600?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0009279722001600?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2022.109955" target="_blank" >10.1016/j.cbi.2022.109955</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dipyridophenazine iridium(III) complex as a phototoxic cancer stem cell selective, mitochondria targeting agent

Popis výsledku v původním jazyce

In this work, the mechanism underlying the anticancer activity of a photoactivatable Ir(III) compound of the type [Ir(C N)2(dppz)][PF6] where C N = 1-methyl-2-(2 '-thienyl)benzimidazole (complex 1) was investigated. Complex 1 photoactivated by visible light shows potent activity against highly aggressive and poorly treatable Rhabdomyosarcoma (RD) cells, the most frequent soft tissue sarcomas of children. This remarkable activity of 1 was observed not only in RD cells cultured in 2D monolayers but, more importantly, also in 3D spheroids, which resemble in many aspects solid tumors and serve as a promising model to mimic the in vivo situation. Importantly, photoactivated 1 kills not only differentiated RD cells but also even more effectively cancer stem cells (CSCs) of RD. One of the factors responsible for the activity of irradiated 1 in RD CSCs is its ability to produce ROS in these cells more effectively than in differentiated RD cells. Moreover, photoactivated 1 caused in RD differentiated cells and CSCs a significant decrease of mitochondrial membrane potential and promotes opening mitochondrial permeability transition pores in these cells, a mechanism that has never been demonstrated for any other metal-based anticancer complex. The results of this work give evidence that 1 has a potential for further evaluation using in vivo models as a promising chemotherapeutic agent for photodynamic therapy of hardly treatable human Rhabdomyosarcoma, particularly for its activity in both stem and differentiated cancer cells.

Název v anglickém jazyce

Dipyridophenazine iridium(III) complex as a phototoxic cancer stem cell selective, mitochondria targeting agent

Popis výsledku anglicky

In this work, the mechanism underlying the anticancer activity of a photoactivatable Ir(III) compound of the type [Ir(C N)2(dppz)][PF6] where C N = 1-methyl-2-(2 '-thienyl)benzimidazole (complex 1) was investigated. Complex 1 photoactivated by visible light shows potent activity against highly aggressive and poorly treatable Rhabdomyosarcoma (RD) cells, the most frequent soft tissue sarcomas of children. This remarkable activity of 1 was observed not only in RD cells cultured in 2D monolayers but, more importantly, also in 3D spheroids, which resemble in many aspects solid tumors and serve as a promising model to mimic the in vivo situation. Importantly, photoactivated 1 kills not only differentiated RD cells but also even more effectively cancer stem cells (CSCs) of RD. One of the factors responsible for the activity of irradiated 1 in RD CSCs is its ability to produce ROS in these cells more effectively than in differentiated RD cells. Moreover, photoactivated 1 caused in RD differentiated cells and CSCs a significant decrease of mitochondrial membrane potential and promotes opening mitochondrial permeability transition pores in these cells, a mechanism that has never been demonstrated for any other metal-based anticancer complex. The results of this work give evidence that 1 has a potential for further evaluation using in vivo models as a promising chemotherapeutic agent for photodynamic therapy of hardly treatable human Rhabdomyosarcoma, particularly for its activity in both stem and differentiated cancer cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA21-27514S" target="_blank" >GA21-27514S: Sloučeniny kovů pro zvýšenou imunoterapii rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

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

360

Číslo periodika v rámci svazku

JUN 1 2022

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

11

Strana od-do

109955

Kód UT WoS článku

000798549900004

EID výsledku v databázi Scopus

2-s2.0-85129251224