Therapeutic Efficacy of Pharmacological Ascorbate on Braf Inhibitor Resistant Melanoma Cells In Vitro and In Vivo.


Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
05 04 2022
Historique:
received: 17 02 2022
revised: 25 03 2022
accepted: 01 04 2022
entrez: 12 4 2022
pubmed: 13 4 2022
medline: 14 4 2022
Statut: epublish

Résumé

High-dose ascorbate paradoxically acts as a pro-oxidant causing the formation of hydrogen peroxide in an oxygen dependent manner. Tumor cells (in particular melanoma cells) show an increased vulnerability to ascorbate induced reactive oxygen species (ROS). Therefore, high-dose ascorbate is a promising pharmacological approach to treating refractory melanomas, e.g., with secondary resistance to targeted BRAF inhibitor therapy. BRAF mutated melanoma cells were treated with ascorbate alone or in combination with the BRAF inhibitor vemurafenib. Viability, cell cycle, ROS production, and the protein levels of phospho-ERK1/2, GLUT-1 and HIF-1α were analyzed. To investigate the treatment in vivo, C57BL/6NCrl mice were subcutaneously injected with D4M.3A (Braf

Identifiants

pubmed: 35406796
pii: cells11071229
doi: 10.3390/cells11071229
pmc: PMC8997901
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Protein Kinase Inhibitors 0
Reactive Oxygen Species 0
Vemurafenib 207SMY3FQT
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Heike Niessner (H)

Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.
Department of Dermatology, Division of Dermatooncology, University of Tuebingen, Liebermeisterstr 25, 72076 Tuebingen, Germany.
Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany.

Markus Burkard (M)

Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.

Christian Leischner (C)

Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.

Olga Renner (O)

Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.

Sarah Plöger (S)

Department of Dermatology, Division of Dermatooncology, University of Tuebingen, Liebermeisterstr 25, 72076 Tuebingen, Germany.

Francisco Meraz-Torres (F)

Department of Dermatology, Division of Dermatooncology, University of Tuebingen, Liebermeisterstr 25, 72076 Tuebingen, Germany.

Matti Böcker (M)

Department of Dermatology, Division of Dermatooncology, University of Tuebingen, Liebermeisterstr 25, 72076 Tuebingen, Germany.

Constanze Hirn (C)

Department of Dermatology, Division of Dermatooncology, University of Tuebingen, Liebermeisterstr 25, 72076 Tuebingen, Germany.

Ulrich M Lauer (UM)

Department of Internal Medicine VIII, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.

Sascha Venturelli (S)

Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.
Department of Vegetative and Clinical Physiology, Institute of Physiology, University of Tuebingen, Wilhelmstraße 56, 72074 Tuebingen, Germany.

Christian Busch (C)

Dermatologie zum Delfin, Stadthausstrasse 12, 8400 Winterthur, Switzerland.

Tobias Sinnberg (T)

Department of Dermatology, Division of Dermatooncology, University of Tuebingen, Liebermeisterstr 25, 72076 Tuebingen, Germany.
Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany.
Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.

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Classifications MeSH