Proscillaridin A is cytotoxic for glioblastoma cell lines and controls tumor xenograft growth in vivo - GlioME: Gliomagenesis and MicroEnvironment Accéder directement au contenu
Article Dans Une Revue Oncotarget Année : 2014

Proscillaridin A is cytotoxic for glioblastoma cell lines and controls tumor xenograft growth in vivo

Emilie Denicolaï
Nathalie Baeza-Kallee
  • Fonction : Auteur
Aurélie Tchoghandjian
  • Fonction : Auteur
Manon Carré
  • Fonction : Auteur
Carole Colin
  • Fonction : Auteur
Carine Jiguet Jiglaire
  • Fonction : Auteur
Sandy Mercurio
  • Fonction : Auteur
Christophe Beclin
  • Fonction : Auteur

Résumé

Glioblastoma is the most frequent primary brain tumor in adults. Because of molecular and cellular heterogeneity, high proliferation rate and significant invasive ability, prognosis of patients is poor. Recent therapeutic advances increased median overall survival but tumor recurrence remains inevitable. In this context, we used a high throughput screening approach to bring out novel compounds with anti-proliferative and anti-migratory properties for glioblastoma treatment. Screening of the Prestwick chemical library® of 1120 molecules identified proscillaridin A, a cardiac glycoside inhibitor of the Na+/K+ ATPase pump, with most significant effects on glioblastoma cell lines. In vitro effects of proscillaridin A were evaluated on GBM6 and GBM9 stem-like cell lines and on U87-MG and U251-MG cell lines. We showed that proscillaridin A displayed cytotoxic properties, triggered cell death, induced G2/M phase blockade in all the glioblastoma cell lines and impaired GBM stem self-renewal capacity even at low concentrations. Heterotopic and orthotopic xenotransplantations were used to confirm in vivo anticancer effects of proscillaridin A that both controls xenograft growth and improves mice survival. Altogether, results suggest that proscillaridin A is a promising candidate as cancer therapies in glioblastoma. This sustains previous reports showing that cardiac glycosides act as anticancer drugs in other cancers.
Fichier principal
Vignette du fichier
oncotarget-v5i21-2541.pdf (7.98 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03637723 , version 1 (18-06-2024)

Licence

Identifiants

Citer

Emilie Denicolaï, Nathalie Baeza-Kallee, Aurélie Tchoghandjian, Manon Carré, Carole Colin, et al.. Proscillaridin A is cytotoxic for glioblastoma cell lines and controls tumor xenograft growth in vivo. Oncotarget, 2014, 5 (21), pp.10934-10948. ⟨10.18632/oncotarget.2541⟩. ⟨hal-03637723⟩
14 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More