Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity
Gobec, Stanislav (Author), Kos, Janko (Author), Mitrović, Ana (Author), Čemažar, Maja (Author), Serša, Gregor (Author), Sosič, Izidor (Author), Mirković, Bojana (Author), Markelc, Boštjan (Author), Turk, Boris (Author), Butinar, Miha (Author), Vasiljeva, Olga (Author)

URLURL - Presentation file, Visit http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3699&path[]=7738 This link opens in a new window

Cathepsin B is a ubiquitously expressed lysosomal cysteine protease that participates in protein turnover within lysosomes. However, its protein and activity levels have been shown to be increased in cancer. Cathepsin B endopeptidase activity is involved in the degradation of extracellular matrix,a process that promotes tumor invasion, metastasis and angiogenesis. Previously, we reported an established antibiotic nitroxoline as a potent and selective inhibitor of cathepsin B. In the present study, we elucidated its anti-tumor properties in in vitro and in vivo tumor models. Tumor and endothelial cell lines with high levels of active cathepsin B were selected for functional analysis of nitroxoline in vitro. Nitroxoline significantly reduced extracellular DQ-collagen IV degradation by all evaluated cancer cell lines using spectrofluorimetry. Nitroxoline also markedly decreased tumor cell invasion monitored in real time and reduced the invasive growth of multicellular tumor spheroids, used as a 3D in vitro model of tumor invasion. Additionally, endothelial tube formation was significantly reduced by nitroxoline in an in vitro angiogenesis assay. Finally, nitroxoline significantly abrogated tumor growth, angiogenesis and metastasis in vivo in LPB fibrosarcoma and MMTV-PyMT breast cancer mouse models. Overall, our results designate nitroxoline as a promising drug candidate for anti-cancer treatment.

Keywords:katepsin B, invazivni tumor, angiogeneza, metastaze, nitroksolin
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 19027-19042
Numbering:Vol. 6, no. 22
ISSN on article:1949-2553
COBISS.SI-ID:3834225 Link is opened in a new window
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Shortened title:Oncotarget
Publisher:Impact Journals
COBISS.SI-ID:3833969 This link opens in a new window

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