Triphenylphosphonium-functionalized N-heterocyclic carbene platinum complexes [(NHC-TPP)Pt] induce cell death of human glioblastoma cancer stem cells.
Fiche publication
Date publication
mai 2023
Journal
International journal of pharmaceutics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BELLEMIN-LAPONNAZ Stéphane, Dr DONTENWILL Monique, Pr FOURNEL Sylvie, Dr FRISCH Benoit, Dr HEURTAULT Béatrice, Dr KICHLER Antoine
Tous les auteurs :
Fernandez de Larrinoa P, Parmentier J, Kichler A, Achard T, Dontenwill M, Herold-Mende C, Fournel S, Frisch B, Heurtault B, Bellemin-Laponnaz S
Lien Pubmed
Résumé
A growing body of experimental and clinical evidence suggests that rare cell populations, known as cancer stem cells (CSCs), play an important role in the development and therapeutic resistance of several cancers, including glioblastoma. Elimination of these cells is therefore of paramount importance. Interestingly, recent results have shown that the use of drugs that specifically disrupt mitochondria or induce mitochondria-dependent apoptosis can efficiently kill cancer stem cells. In this context, a novel series of platinum(II) complexes bearing N-heterocyclic carbene (NHC) of the type [(NHC)PtI2(L)] modified with the mitochondria targeting group triphenylphosphonium were synthesized. After a complete characterization of the platinum complexes, the cytotoxicity against two different cancer cell lines, including a cancer stem cell line, was investigated. The best compound reduced the cell viability of both cell lines by 50% in the mM range, with an approximately 300-fold higher anticancer activity on the CSC line compared to oxaliplatin. Finally, mechanistic studies showed that the triphenylphosphonium functionalized platinum complexes significantly altered mitochondrial function and also induced atypical cell death.
Mots clés
Glioblastoma, N-Heterocylic Carbenes platinum complexes, cancer stem cells, cytotoxicity, mitochondria, triphenylphosphonium moiety
Référence
Int J Pharm. 2023 05 25;:123071