title: Slowing down glioblastoma progression in mice by running or the anti-malarial drug dihydroartemisinin? Induction of oxidative stress in murine glioblastoma therapy.
abstract: Influencing cancer metabolism by lifestyle changes is an attractive strategy as - if effective - exercise-induced problems may be less severe than those induced by classical anti-cancer therapies. Pursuing this idea, clinical trials evaluated the benefit of e.g. different diets such as the ketogenic diet, intermittent caloric restriction and physical exercise (PE) in the primary and secondary prevention of different cancer types. PE proved to be beneficial in the context of breast and colon cancer.Glioblastoma has a dismal prognosis, with an average overall survival of about one year despite maximal safe resection, concomitant radiochemotherapy with temozolomide followed by adjuvant temozolomide therapy. Here, we focused on the influence of PE as an isolated and adjuvant treatment in murine GB therapy.PE did not reduce toxic side effects of chemotherapy in mice administered in a dose escalating scheme as shown before for starvation. Although regular treadmill training on its own had no obvious beneficial effects, its combination with temozolomide was beneficial in the treatment of glioblastoma-bearing mice. As PE might partly act through the induction of reactive oxygen species, dihydroartemisinin - an approved anti-malarial drug which induces oxidative stress in glioma cells - was further evaluated in vitro and in vivo. Dihydroartemisinin showed anti-glioma activity by promoting autophagy, reduced the clonogenic survival and proliferation capacity of glioma cells, and prolonged the survival of tumor bearing mice. Using the reactive oxygen species scavenger n-acetyl-cysteine these effects were in part reversible, suggesting that dihydroartemisinin partly acts through the generation of reactive oxygen species.
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lemke
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Pledl
authors.affiliation: Central Laboratory of Heidelberg University Hospital, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zorn
authors.affiliation: Core Facility Small Animal Imaging Center, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jugold
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ed
authors.initials: E
authors.lastname: Green
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Blaes
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Löw
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Hertenstein
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Ott
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Neuropathology, Institute of Pathology, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ann-Catherine
authors.initials: AC
authors.lastname: Steffen
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Weiler
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Winkler
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Neurology Clinic and National Center for Tumor Diseases, University of Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077204:Temozolomide
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D017382:Reactive Oxygen Species; C039060:artenimol; D003606:Dacarbazine; D000077204:Temozolomide
keywords: dihydroartemisinin; glioblastoma; physical exercise; physical exercises (PE); therapy