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Targeting the cancer stem cell (CSC) metabolism with designed, reactive metal complexes

Project description

Novel metal compounds as anti-cancer agents

A G-quadruplex is a four-stranded nucleic acid secondary structure formed in G nucleotide-rich regions of the DNA or RNA. Emerging evidence implicates these structures in cancer growth and progression. With this in mind, the EU-funded antiCSC project proposes to develop metal-based compounds that have the capacity to interact with accessible guanines present in adjacent positions to these self-assembled structures, and thereby alter their conformation and function. Preliminary results indicate that these compounds suppress the stemness of cancer stem cells by interfering with mitochondrial respiration. The antiCSC proposal will determine the mechanism underlying the action of these metal compounds and exploit their potential as novel anti-cancer agents.

Objective

Designed, bulky metal complexes with a labile coordination position react with accessible guanines at G4 DNA quadruplexes, promoting changes in their conformation and function. Importantly, we have found that this selective reactivity leads to very interesting biological effects. In particular, some of these compounds are able to suppress the “stem”-like character of cancer stem cells, apparently by deterring their mitochondrial respiration. Preliminary experiments, including in vivo assays, confirm that these biological effects result in remarkable antitumoral activities. This proposal aims to explore the scope of the approach, confirm that the mechanism of action involves mitochondria, design more selective versions and exploit the potential of the compounds as new type of anticancer agents.

Host institution

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Net EU contribution
€ 130 000,00
Address
COLEXIO DE SAN XEROME PRAZA DO OBRADOIRO S/N
15782 Santiago De Compostela
Spain

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Region
Noroeste Galicia A Coruña
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Beneficiaries (2)