Implementation of a combined CDK inhibition and arginine-deprivation approach to target arginine-auxotrophic glioblastoma multiforme cells

Christin Riess; Katharina del Moral; Adina Fiebig; Philipp Kaps; Charlotte Linke; Burkhard Hinz; Anne Rupprecht; Marcus Frank; Tomas Fiedler; Dirk Koczan; Sascha Troschke-Meurer; Holger N. Lode; Nadja Engel; Thomas Freitag; Carl Friedrich Classen; Claudia Maletzki

doi:10.1038/s41419-022-05006-1

Cell Death and Disease (Jun 2022)

Implementation of a combined CDK inhibition and arginine-deprivation approach to target arginine-auxotrophic glioblastoma multiforme cells

Christin Riess,
Katharina del Moral,
Adina Fiebig,
Philipp Kaps,
Charlotte Linke,
Burkhard Hinz,
Anne Rupprecht,
Marcus Frank,
Tomas Fiedler,
Dirk Koczan,
Sascha Troschke-Meurer,
Holger N. Lode,
Nadja Engel,
Thomas Freitag,
Carl Friedrich Classen,
Claudia Maletzki

Affiliations

Christin Riess: University Children’s Hospital, Rostock University Medical Center
Katharina del Moral: University Children’s Hospital, Rostock University Medical Center
Adina Fiebig: Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center
Philipp Kaps: University Children’s Hospital, Rostock University Medical Center
Charlotte Linke: University Children’s Hospital, Rostock University Medical Center
Burkhard Hinz: Institute for Pharmacology and Toxicology, Rostock University Medical Center
Anne Rupprecht: Institute for Pharmacology and Toxicology, Rostock University Medical Center
Marcus Frank: Medical Biology and Electron Microscopy Center, Rostock University Medical Center
Tomas Fiedler: Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center
Dirk Koczan: Institute for Immunology, University of Rostock
Sascha Troschke-Meurer: Department of Pediatric Oncology and Hematology, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse
Holger N. Lode: Department of Pediatric Oncology and Hematology, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse
Nadja Engel: Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center
Thomas Freitag: Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center
Carl Friedrich Classen: University Children’s Hospital, Rostock University Medical Center
Claudia Maletzki: Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center

DOI: https://doi.org/10.1038/s41419-022-05006-1
Journal volume & issue: Vol. 13, no. 6
pp. 1 – 14

Abstract

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The complex effects of combined CDki/SPyADI application on arginine-auxotrophic glioblastoma multiforme cells. CDki/SPyADI combination therapy impairs cell proliferation, invasiveness, gene expression, induces mitochondrial impairment, and vacuole formation. Abemaciclib-SPyADI-treatment suppresses DNA repair, dinaciclib-SpyADI-treatment enhances γ-H2AX accumulation and activates the stress sensor GADD45 and β-catenin antagonist AXIN2. Both CDKi/SpyADI combinations significantly boost cell death.

Published in Cell Death and Disease

ISSN: 2041-4889 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/cddis/index.html

About the journal