Ferroquine, the next generation antimalarial drug, has antitumor activity

被引：75

作者：

Kondratskyi, Artem ^{[1
]}

Kondratska, Kateryna ^{[1
]}

Abeele, Fabien Vanden ^{[1
]}

Gordienko, Dmitri ^{[1
]}

Dubois, Charlotte ^{[1
,5
,6
]}

Toillon, Robert-Allain ^{[2
]}

Slomianny, Christian ^{[1
]}

Lemiere, Sebastien ^{[3
]}

Delcourt, Philippe ^{[1
]}

Dewailly, Etienne ^{[1
]}

Skryma, Roman ^{[1
]}

Biot, Christophe ^{[4
]}

Prevarskaya, Natalia ^{[1
]}

机构：

[1] Univ Lille 1, SIRIC ONCOLille, INSERM, U1003,Lab Excellence Ion Channels Sci & Therapeut, Villeneuve Dascq, France

[2] Univ Lille 1, INSERM, U908, Villeneuve Dascq, France

[3] Univ Lille 1, Univ Lille Nord France, EA 4515, LGCgE,Cite Sci,SN3, F-59655 Villeneuve Dascq, France

[4] Univ Lille 1, CNRS, UGSF, UMR 8576, F-59650 Villeneuve Dascq, France

[5] Katholieke Univ Leuven, Vesalius Res Ctr, Lab Angiogenesis & Vasc Metab, Dept Oncol, Campus Gasthuisberg O&N4,Herestr 49-912, B-3000 Leuven, Belgium

[6] Vesalius Res Ctr VIB, Campus Gasthuisberg O&N4,Herestr 49-912, B-3000 Leuven, Belgium

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

LYSOSOMAL MEMBRANE PERMEABILIZATION; TUMOR-CELLS; AUTOPHAGY; CHLOROQUINE; HYPOXIA; DEGRADATION; MECHANISM; IMAGE;

D O I：

10.1038/s41598-017-16154-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-1 alpha (HIF-1 alpha) 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.

引用

页数：15