In Cellulo Evaluation of the Therapeutic Potential of NHC Platinum Compounds in Metastatic Cutaneous Melanoma.
Fiche publication
Date publication
octobre 2020
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BELLEMIN-LAPONNAZ Stéphane
Tous les auteurs :
Charignon E, Bouché M, Clave-Darcissac C, Dahm G, Ichim G, Clotagatide A, Mertani HC, Telouk P, Caramel J, Diaz JJ, Bellemin-Laponnaz S, Bouvet P, Billotey C
Lien Pubmed
Résumé
We describe here the evaluation of the cytotoxic efficacy of two platinum (II) complexes bearing an N-heterocyclic carbene (NHC) ligand, a pyridine ligand and bromide or iodide ligands on a panel of human metastatic cutaneous melanoma cell lines representing different genetic subsets including BRAF-inhibitor-resistant cell lines, namely A375, SK-MEL-28, MeWo, HMCB, A375-R, SK-MEL-5-R and 501MEL-R. Cisplatin and dacarbazine were also studied for comparison purposes. Remarkably, the iodine-labelled Pt-NHC complex strongly inhibited proliferation of all tested melanoma cells after 1-h exposure, likely due to its rapid uptake by melanoma cells. The mechanism of this inhibitory activity involves the formation of DNA double-strand breaks and apoptosis. Considering the intrinsic chemoresistance of metastatic melanoma cells of current systemic treatments, these findings are promising and could give research opportunities in the future to improve the prognosis of patients suffering from unresectable metastatic melanoma that are not eligible or that do not respond to the most effective drugs available to date, namely BRAF inhibitors and the anti-PD-1 monoclonal antibody (mAb).
Mots clés
BRAF inhibitor resistance, apoptosis, chemoresistance, chemotherapy, metastatic cutaneous melanoma, platinum N-heterocyclic carbene complexes
Référence
Int J Mol Sci. 2020 Oct 22;21(21):