An N-heterocyclic carbene iridium(III) complex as a potent anti-cancer stem cell therapeutic.

Fiche publication

Date publication

septembre 2022

Journal

Chemico-biological interactions

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DONTENWILL Monique , Pr FOURNEL Sylvie , Dr KICHLER Antoine

Tous les auteurs :
McCartin C, Mathieu E, Dontenwill M, Herold-Mende C, Idbaih A, Bonfiglio A, Mauro M, Fournel S, Kichler A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36087816

Résumé

Cancer stem cells (CSCs) represent a difficult to treat cellular niche within tumours due to their unique characteristics, which give them a high propensity for resistance to classical anti-cancer treatments and the ability to re-populate the tumour mass. An attribute that may be implicated in the high rates of recurrence of certain tumours. However, other characteristics specific to these cells, such as their high dependence on mitochondria, may be exploited for the development of new therapeutic agents that are effective against the niche. As such, a previously described phosphorescent N-heterocyclic carbene iridium(III) compound which showed a high level of cytotoxicity against classical tumour cell lines with mitochondria-specific effects was studied for its potential against CSCs. The results showed a significantly higher level of activity against several CSC lines compared to non-CSCs. Mitochondrial localisation and superoxide production was confirmed. Although the cell death involved caspase activation, their role in cell death was not definitive, with a potential implication of other, non-apoptotic pathways shown. A cytostatic effect of the compound was also displayed at low mortality doses. This study thus provides important insights into the mechanisms and the potential for this class of molecule in the domain of anti-CSC therapeutics.