Ferroquine, the next generation antimalarial drug, has antitumor activity

Despite the tremendous progress in medicine, cancer remains one of the most serious global health problems awaiting new effective therapies. Here we present ferroquine (FQ), the next generation antimalarial drug, as a promising candidate for repositioning as cancer therapeutics. We report that FQ po...

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Published in:Scientific reports 2017-11, Vol.7 (1), p.15896-15, Article 15896
Main Authors: Kondratskyi, Artem, Kondratska, Kateryna, Vanden Abeele, Fabien, Gordienko, Dmitri, Dubois, Charlotte, Toillon, Robert-Allain, Slomianny, Christian, Lemière, Sébastien, Delcourt, Philippe, Dewailly, Etienne, Skryma, Roman, Biot, Christophe, Prevarskaya, Natalia
Format: Article
Language:English
Subjects:
AKT protein
Antimalarial agents
Antitumor activity
Cancer
Caspase
Cell death
Chloroquine
Depolarization
Hypoxia-inducible factors
Lysosomes
Membrane potential
Mitochondria
Phagocytosis
Prostate
Prostate cancer
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Summary:Despite the tremendous progress in medicine, cancer remains one of the most serious global health problems awaiting new effective therapies. Here we present ferroquine (FQ), the next generation antimalarial drug, as a promising candidate for repositioning as cancer therapeutics. We report that FQ potently inhibits autophagy, perturbs lysosomal function and impairs prostate tumor growth in vivo. We demonstrate that FQ negatively regulates Akt kinase and hypoxia-inducible factor-1α (HIF-1α) and is particularly effective in starved and hypoxic conditions frequently observed in advanced solid cancers. FQ enhances the anticancer activity of several chemotherapeutics suggesting its potential application as an adjuvant to existing anticancer therapy. Alike its parent compound chloroquine (CQ), FQ accumulates within and deacidifies lysosomes. Further, FQ induces lysosomal membrane permeabilization, mitochondrial depolarization and caspase-independent cancer cell death. Overall, our work identifies ferroquine as a promising new drug with a potent anticancer activity.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-16154-2