Pyridazinone Derivatives Limit Osteosarcoma-Cells Growth In Vitro and In Vivo.
Fiche publication
Date publication
novembre 2021
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GANGLOFF Sophie, Pr SAPI Janos, Dr VELARD Frédéric, Dr AUDONNET Sandra , Dr GERARD Stéphane, Dr COCHARD Marie
Tous les auteurs :
Moniot A, Braux J, Bour C, Guillaume C, Lamret F, Allart-Simon I, Audonnet S, Renault S, Rédini F, Laronze-Cochard M, Sapi J, Gangloff SC, Gérard S, Velard F
Lien Pubmed
Résumé
Osteosarcoma is a rare primary bone cancer that mostly affects children and young adults. Current therapeutic approaches consist of combining surgery and chemotherapy but remain unfortunately insufficient to avoid relapse and metastases. Progress in terms of patient survival has remained the same for 30 years. In this study, novel pyridazinone derivatives have been evaluated as potential anti-osteosarcoma therapeutics because of their anti-type 4 phosphodiesterase activity, which modulates the survival of several other cancer cells. By using five-four human and one murine osteosarcoma-cell lines, we demonstrated differential cytotoxic effects of four pyridazinone scaffold-based compounds (mitochondrial activity and DNA quantification). Proapoptotic (annexin V positive cells and caspase-3 activity), anti-proliferative (EdU integration) and anti-migratory effects (scratch test assay) were also observed. Owing to their cytotoxic activity in in vitro conditions and their ability to limit tumor growth in a murine orthotopic osteosarcoma model, our data suggest that these pyridazinone derivatives might be hit-candidates to develop new therapeutic strategies against osteosarcoma.
Mots clés
cytotoxicity, migration, osteosarcoma, pyridazinone, tumor growth
Référence
Cancers (Basel). 2021 Nov 28;13(23):