The iron chelator and OXPHOS inhibitor VLX600 induces mitophagy and an autophagy-dependent type of cell death in glioblastoma cells-Reference-Cited by-同舟云学术

The iron chelator and OXPHOS inhibitor VLX600 induces mitophagy and an autophagy-dependent type of cell death in glioblastoma cells

Published:2023-12-01 Issue:6 Volume:325 Page:C1451-C1469
ISSN:0363-6143
Container-title:American Journal of Physiology-Cell Physiology
language:en
Short-container-title:American Journal of Physiology-Cell Physiology

Author:

Reisbeck Lisa¹,Linder Benedikt¹,Tascher Georg²,Bozkurt Süleyman²,Weber Katharina J.³⁴⁵⁶,Herold-Mende Christel⁷,van Wijk Sjoerd J. L.⁸⁶,Marschalek Rolf⁹^ORCID,Schaefer Liliana¹⁰^ORCID,Münch Christian²,Kögel Donat¹⁶^ORCID

Affiliation:

1. Experimental Neurosurgery, Department of Neurosurgery, Neuroscience Center, Goethe University Hospital, Frankfurt am Main, Germany

2. Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany

3. Neurological Institute (Edinger Institute), Goethe University Hospital, Frankfurt am Main, Germany

4. Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany

5. University Cancer Center Frankfurt (UCT), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany

6. German Cancer Consortium (DKTK), Partner site Frankfurt/Main, a partnership between DKFZ and University Hospital, Frankfurt, Germany

7. Division of Experimental Neurosurgery, Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany

8. Institute for Pediatric Hematology and Oncology, Goethe University Hospital Frankfurt/Main, Frankfurt am Main, Germany

9. Institute of Pharmaceutical Biology, Diagnostic Center of Acute Leukemia, University of Frankfurt, Frankfurt/Main, Germany

10. Institute of Pharmacology and Toxicology, Goethe University, Frankfurt, Germany

Abstract

Induction of cell-lethal autophagy represents a possible strategy to combat glioblastoma (GBM). Here, we demonstrate that the novel iron chelator and OXPHOS inhibitor VLX600 exerts pronounced tumor cell-killing effects in adherently cultured GBM cells and glioblastoma stem-like cell (GSC) spheroid cultures that depend on the iron-chelating function of VLX600 and on autophagy activation, underscoring the context-dependent role of autophagy in therapy responses. VLX600 represents an interesting novel drug candidate for the treatment of this tumor.

Funder

Deutsche Forschungsgemeinschaft

Deutsche Krebshilfe

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpcell.00293.2023

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