An N-heterocyclic carbene iridium(III) complex as a potent anti-cancer stem cell therapeutic

McCartin, Conor; Mathieu, Eric; Dontenwill, Monique; Herold‐Mende, Christel; Idbaïh, Ahmed; Bonfiglio, Anna; Mauro, Matteo; Fournel, Sylvie; Kichler, Antoine

doi:10.1016/j.cbi.2022.110167

Cited by 4 publications

(2 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect on viability was measured (four days following seeding to allow the formation of spheroids) via ATP decrease using the CelltiterGlo 3D cell viability assay following 24 h treatment and was compared to a more differentiated glioma cell line (U87-MG) and a primary non-cancerous stem cell culture, DPSCs (grown as spheres ( Figure S1 )) ( Table 1 and Figures S2–S6 ). The commercial platinum-based anti-cancer therapeutic oxaliplatin, and the standard glioblastoma treatment, temozolomide, were used for comparison (previously published results in [ 45 ]).…”

Section: Resultsmentioning

confidence: 99%

Polyethylenimine, an Autophagy-Inducing Platinum-Carbene-Based Drug Carrier with Potent Toxicity towards Glioblastoma Cancer Stem Cells

McCartin

Dussouillez

Bernhard

et al. 2022

Cancers

View full text Add to dashboard Cite

The difficulty involved in the treatment of many tumours due to their recurrence and resistance to chemotherapy is tightly linked to the presence of cancer stem cells (CSCs). This CSC sub-population is distinct from the majority of cancer cells of the tumour bulk. Indeed, CSCs have increased mitochondrial mass that has been linked to increased sensitivity to mitochondrial targeting compounds. Thus, a platinum-based polyethylenimine (PEI) polymer–drug conjugate (PDC) was assessed as a potential anti-CSC therapeutic since it has previously displayed mitochondrial accumulation. Our results show that CSCs have increased specific sensitivity to the PEI carrier and to the PDC. The mechanism of cell death seems to be necrotic in nature, with an absence of apoptotic markers. Cell death is accompanied by the induction of a protective autophagy. The interference in the balance of this pathway, which is highly important for CSCs, may be responsible for a partial reversion of the stem-like phenotype observed with prolonged PEI and PDC treatment. Several markers also indicate the cell death mode to be capable of inducing an anti-cancer immune response. This study thus indicates the potential therapeutic perspectives of polycations against CSCs.

show abstract

Section: Resultsmentioning

confidence: 99%

Polyethylenimine, an Autophagy-Inducing Platinum-Carbene-Based Drug Carrier with Potent Toxicity towards Glioblastoma Cancer Stem Cells

McCartin

Dussouillez

Bernhard

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…We thus reiterate and emphasise our previous warning regarding the comparison of toxicities between cell lines with vastly different culture media [ 31 ], which is especially pertinent in the CSC domain due to the media required for the maintenance of their stem-like phenotype [ 39 , 40 , 41 , 42 ]. Although, at least in this case, the phenomenon seems to be restricted to cationic polymers (or at least to not be generally applicable to all molecules), as an iridium compound previously assessed for its action as an anti-CSC therapeutic by our team did not display a culture medium-dependent change in toxicity on U87 cells ( Figure S7 ) [ 39 ]. The effect of CSC-specific toxicity thus appeared to be a 22 kDa L-PEI-specific effect rather than a general effect applicable to all polycations.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Cytotoxicity of Cationic Polymers on Glioblastoma Cancer Stem Cells

McCartin

Blumberger

Dussouillez

et al. 2022

JFB

Self Cite

View full text Add to dashboard Cite

Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug conjugates (PDCs). Yet a potentially underexplored domain of research is in their inherent potential as anti-cancer therapeutic agents, which has been indicated by several studies. Even more interesting is the recent observation that certain polycations may present a significantly greater toxicity towards the clinically important cancer stem cell (CSC) niche than towards more differentiated bulk tumour cells. These cells, which possess the stem-like characteristics of self-renewal and differentiation, are highly implicated in cancer drug resistance, tumour recurrence and poor clinical prognosis. The search for compounds which may target and eliminate these cells is thus of great research interest. As such, the observation in our previous study on a PEI-based PDC which showed a considerably higher toxicity of PEI towards glioblastoma CSCs (GSCs) than on more differentiated glioma (U87) cells led us to investigate other cationic polymers for a similar effect. The evaluation of the toxicity of a range of different types of polycations, and an investigation into the potential source of GSC’s sensitivity to such compounds is thus described.

show abstract

Effect of fluorination on the cytotoxic potentials of benzimidazolium-based N-heterocyclic carbene ligands and their silver(I) complexes

Wong,

Khor,

Anak Inggang

et al. 2024

Inorganica Chimica Acta

View full text Add to dashboard Cite

An N-heterocyclic carbene iridium(III) complex as a potent anti-cancer stem cell therapeutic

Cited by 4 publications

References 52 publications

Polyethylenimine, an Autophagy-Inducing Platinum-Carbene-Based Drug Carrier with Potent Toxicity towards Glioblastoma Cancer Stem Cells

Polyethylenimine, an Autophagy-Inducing Platinum-Carbene-Based Drug Carrier with Potent Toxicity towards Glioblastoma Cancer Stem Cells

Evaluation of the Cytotoxicity of Cationic Polymers on Glioblastoma Cancer Stem Cells

Effect of fluorination on the cytotoxic potentials of benzimidazolium-based N-heterocyclic carbene ligands and their silver(I) complexes

Contact Info

Product

Resources

About