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Sci Rep. 2017 Nov 21;7(1):15896. doi: 10.1038/s41598-017-16154-2.

Ferroquine, the next generation antimalarial drug, has antitumor activity.

Author information

1
Inserm, U-1003, Laboratory of Excellence, Ion Channels Science and Therapeutics, SIRIC ONCOLille, Université Lille 1, Villeneuve d'Ascq, France. Artem.Kondratskyi@inserm.fr.
2
Inserm, U-1003, Laboratory of Excellence, Ion Channels Science and Therapeutics, SIRIC ONCOLille, Université Lille 1, Villeneuve d'Ascq, France.
3
Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Department of Oncology (KU Leuven) and Vesalius Research Center (VIB), Campus Gasthuisberg O&N4, Herestraat 49 - 912, B-3000, Leuven, Belgium.
4
Inserm U908, Université Lille 1, Villeneuve d'Ascq, France.
5
Univ. Lille Nord de France, EA 4515 - LGCgE - Université Lille 1, Cité scientifique, SN3, F-59655, Villeneuve d'Ascq, France.
6
Univ. Lille 1, UGSF, UMR 8576 CNRS, 59650, Villeneuve d'Ascq, France.
7
Inserm, U-1003, Laboratory of Excellence, Ion Channels Science and Therapeutics, SIRIC ONCOLille, Université Lille 1, Villeneuve d'Ascq, France. Natacha.Prevarskaya@univ-lille1.fr.

Abstract

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.

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