Gallium(III) Complex with Cloxyquin Ligands Induces Ferroptosis in Cancer Cells and Is a Potent Agent against Both Differentiated and Tumorigenic Cancer Stem Rhabdomyosarcoma Cells
Monika Hreusova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorVojtech Novohradsky
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorLenka Markova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorHana Kostrhunova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorIvan Potočňák
Department of Inorganic Chemistry, Institute of Chemistry, P.J. Šafárik University in Košice, Košice 04001, Slovakia
Search for more papers by this authorViktor Brabec
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Olomouc 78371, Czech Republic
Search for more papers by this authorCorresponding Author
Jana Kasparkova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorMonika Hreusova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorVojtech Novohradsky
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorLenka Markova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorHana Kostrhunova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorIvan Potočňák
Department of Inorganic Chemistry, Institute of Chemistry, P.J. Šafárik University in Košice, Košice 04001, Slovakia
Search for more papers by this authorViktor Brabec
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Olomouc 78371, Czech Republic
Search for more papers by this authorCorresponding Author
Jana Kasparkova
Czech Academy of Sciences, Institute of Biophysics, Brno-61265, Czech Republic cas.cz
Search for more papers by this authorAbstract
In this work, gallium(III) complex with cloxyquin (5-chloro-8-quinolinol, HClQ) ligands is shown to effectively inhibit proliferation of rhabdomyosarcoma cells, the frequent, aggressive, and poorly treatable cancer of children. It offers striking selectivity to cancer cells compared to noncancerous human fibroblasts. The data reveal that the complex induces ferroptosis in rhabdomyosarcoma cells, likely due to interfering with iron metabolism. Importantly, it can kill both bulk and stem rhabdomyosarcoma cells. To the best of our knowledge, this is the first compound based on metal other than Fe capable of inducing ferroptosis in cancer cells.
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this article.
Open Research
Data Availability
All data used to support the findings of this study are included within the article.
Supporting Information
Filename | Description |
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bca3095749-sup-0001-f1.pdfPDF document, 1.1 MB | Supplementary Materials Figure S1: Emission fluorescence spectra of 1 and free cloxyquin (HClQ). Figure S2: Flow cytometry-based profiling of autophagy in RD cells. Figure S3: Detection of ROS in RD cells by flow cytometry. Figure S4: Histograms of lipid peroxidation in RD cells analyzed by flow cytometry. Figure S5: Bright-field images of the rhabdospheres formed from RD CD133+ and RD CD133-cells. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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