Light activation of cyclometalated ruthenium complexes drives towards caspase 3 dependent apoptosis in gastric cancer cells
| Autor: | Jorge Andrés Solís-Ruiz, Anaïs Barthe, Rafael Omar Saavedra-Díaz, Ronan Le Lagadec, Christian Gaiddon, Gilles Riegel |
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| Přispěvatelé: | Université de Strasbourg, INSERM UMR_S 11113 IRFAC, Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2020 |
| Předmět: |
Light
DNA damage [SDV]Life Sciences [q-bio] chemistry.chemical_element Apoptosis Caspase 3 010402 general chemistry 01 natural sciences Biochemistry Ruthenium Inorganic Chemistry chemistry.chemical_compound Stomach Neoplasms Cell Line Tumor Humans [CHIM]Chemical Sciences Mode of action ComputingMilieux_MISCELLANEOUS Caspase chemistry.chemical_classification Reactive oxygen species biology 010405 organic chemistry Singlet oxygen Biological activity Caspase Inhibitors Neoplasm Proteins 0104 chemical sciences chemistry biology.protein Biophysics |
| Zdroj: | Journal of Inorganic Biochemistry Journal of Inorganic Biochemistry, Elsevier, 2020, 208, pp.111080. ⟨10.1016/j.jinorgbio.2020.111080⟩ |
| ISSN: | 0162-0134 |
| Popis: | 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 IC50 in the nanomolar range upon illumination. In particular, we showed that these complexes are particularly active (IC50 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. |
| Databáze: | OpenAIRE |
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