Dipyridophenazine iridium(III) complex as a phototoxic cancer stem cell selective, mitochondria targeting agent
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Dipyridophenazine iridium(III) complex as a phototoxic cancer stem cell selective, mitochondria targeting agent
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA21-27514S" target="_blank" >GA21-27514S: Metal-based compounds for enhanced cancer immunotherapy</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemico-Biological Interactions
ISSN
0009-2797
e-ISSN
1872-7786
Volume of the periodical
360
Issue of the periodical within the volume
JUN 1 2022
Country of publishing house
IE - IRELAND
Number of pages
11
Pages from-to
109955
UT code for WoS article
000798549900004
EID of the result in the Scopus database
2-s2.0-85129251224