2. Academic Validation
  3. Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron

Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron

  • Antioxidants (Basel). 2024 Sep 10;13(9):1095. doi: 10.3390/antiox13091095.
Alban Piotrowsky 1,  Markus Burkard 1,  Katharina Hammerschmidt 1,  Hannah K Ruple 1,  Pia Nonnenmacher 1,  Monika Schumacher 1,  Christian Leischner 1,  Susanne Berchtold 2,  Luigi Marongiu 1 3,  Thomas A Kufer 4,  Ulrich M Lauer 2 5,  Olga Renner 1 6,  Sascha Venturelli 1 7
Affiliations

Affiliations

  • 1 Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstrasse 30, 70599 Stuttgart, Germany.
  • 2 Department of Medical Oncology and Pneumology, Virotherapy Center Tuebingen (VCT), Medical University Hospital, 72076 Tuebingen, Germany.
  • 3 HoLMiR-Hohenheim Center for Livestock Microbiome Research, University of Hohenheim, Garbenstrasse 30, 70599 Stuttgart, Germany.
  • 4 Department of Immunology, Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstrasse 12, 70593 Stuttgart, Germany.
  • 5 German Cancer Consortium (DKTK), Partner Site Tuebingen, a Partnership between DKFZ and University Hospital Tuebingen, 72076 Tuebingen, Germany.
  • 6 Faculty of Food and Nutrition Sciences, Hochschule Niederrhein, University of Applied Sciences, Rheydter Strasse 277, 41065 Moenchengladbach, Germany.
  • 7 Department of Vegetative and Clinical Physiology, Institute of Physiology, University of Tuebingen, Wilhelmstrasse 56, 72074 Tuebingen, Germany.
PMID: 39334754 DOI: 10.3390/antiox13091095
Abstract

Several studies have demonstrated, both in vitro and in animal models, the anti-tumor efficacy of high-dose ascorbate treatment against a variety of tumor entities, including glioblastoma, the most common and aggressive primary malignant brain tumor. The aim of this study was to investigate the effects of high-dose ascorbate as well as dehydroascorbic acid on human glioblastoma cell lines and to evaluate different treatment conditions for the combined administration of ascorbate with magnesium (Mg2+) and iron (Fe3+). Intracellular levels of Reactive Oxygen Species and the induction of cell death following ascorbate treatment were also investigated. We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed for dehydroascorbic acid. Ascorbate-induced cell death was independent of Apoptosis. Both the reduction in cell viability and the ascorbate-induced generation of intracellular Reactive Oxygen Species could be significantly increased by incubating the cells with Fe3+ before ascorbate treatment. This work demonstrates, for the first time, an increase in ascorbate-induced intracellular ROS formation and cytotoxicity in human glioblastoma cells by pre-treatment of the tumor cells with ferric iron, as well as Caspase-3 independence of cell death induced by high-dose ascorbate. Instead, the cell death mechanism caused by high-dose ascorbate in glioblastoma cells shows evidence of Ferroptosis. The results of the present work provide insights into the efficacy and mode of action of pharmacological ascorbate for the therapy of glioblastoma, as well as indications for possible approaches to increase the effectiveness of ascorbate treatment.

Keywords

ascorbate; cancer; glioblastoma; iron; reactive oxygen species; vitamin C.

Figures
Products