Light activation of cyclometalated ruthenium complexes drives towards caspase 3 dependent apoptosis in gastric cancer cells.
Fiche publication
Date publication
mars 2020
Journal
Journal of inorganic biochemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian
Tous les auteurs :
Solís-Ruiz JA, Barthe A, Riegel G, Saavedra-Díaz RO, Gaiddon C, Le Lagadec R
Lien Pubmed
Résumé
Polypyridyl ruthenium complexes have been intensively investigated for their remarkable antiproliferative properties and some are currently being tested in clinical trials. Here, we investigated the impact of illumination on the biological properties of a series of new cyclometalated ruthenium compounds with increased π-conjugation. We determined that various of these complexes display a bivalent biological activity as they are highly cytotoxic by themselves in absence of light while their cytotoxicity can significantly be elevated towards an IC in the nanomolar range upon illumination. In particular, we showed that these complexes are particularly active (IC < 1 μM) on two gastric cancer cell lines (AGS, KATO III) that are resistant towards cisplatin (IC > 25 μM). As expected, light activation leads to increased production of singlet oxygen species in vitro and accumulation of reactive oxygen species in vivo. Importantly, we established that light exposure shifts the mode of action of the complexes towards activation of a caspase 3-dependent apoptosis that correlates with increased DNA damage. Altogether, this study characterizes novel ruthenium complexes with dual activity that can be tuned towards different mode of action in order to bypass cancer cell resistance mechanisms.
Mots clés
Cyclometalation, DNA damage, Gastric cancer, Photoactivation, Ruthenium
Référence
J. Inorg. Biochem.. 2020 Mar 28;208:111080