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Triphenylphosphonium-functionalized N-heterocyclic carbene platinum complexes ((NHC-TPP+)Pt) induce cell death of human glioblastoma cancer stem cells

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 importanc...

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Main Authors: De Larrinoa, Patricia Fernandez (Author) , Parmentier, Jordan (Author) , Kichler, Antoine (Author) , Achard, Thierry (Author) , Dontenwill, Monique (Author) , Herold-Mende, Christel (Author) , Fournel, Sylvie (Author) , Frisch, Benoît (Author) , Heurtault, Béatrice (Author) , Bellemin-Laponnaz, Stéphane (Author)
Format: Article (Journal)
Language:English
Published: 31 May 2023
In: International journal of pharmaceutics
Year: 2023, Volume: 641, Pages: 1-12
ISSN:1873-3476
DOI:10.1016/j.ijpharm.2023.123071
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ijpharm.2023.123071
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S037851732300491X
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Author Notes:Patricia Fernandez de Larrinoa, Jordan Parmentier, Antoine Kichler, Thierry Achard, Monique Dontenwill, Christel Herold-Mende, Sylvie Fournel, Benoît Frisch, Béatrice Heurtault, Stéphane Bellemin-Laponnaz
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Summary: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 low μM 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.
Item Description:Im Text ist "+" hochgestellt
Online verfügbar 25 May 2023, Version des Artikels 31 May 2023
Gesehen am 21.09.2023
Physical Description:Online Resource
ISSN:1873-3476
DOI:10.1016/j.ijpharm.2023.123071

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