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

https://www.ncbi.nlm.nih.gov/pubmed/37244463

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.