New potential biomarker for stratification of patients for pharmacological vitamin C in adjuvant settings of cancer therapy

Rumiana Bakalova; Zhivko Zhelev; Thomas Miller; Ichio Aoki; Tatsuya Higashi

doi:10.1016/j.redox.2019.101357

New potential biomarker for stratification of patients for pharmacological vitamin C in adjuvant settings of cancer therapy

Redox Biol. 2020 Jan:28:101357. doi: 10.1016/j.redox.2019.101357. Epub 2019 Oct 23.

Authors

Rumiana Bakalova¹, Zhivko Zhelev², Thomas Miller³, Ichio Aoki⁴, Tatsuya Higashi⁵

Affiliations

¹ Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan; Group of Quantum-state Controlled MRI, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan. Electronic address: bakalova.rumiana@qst.go.jp.
² Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria; Medical Faculty, Trakia University, Stara Zagora, Bulgaria.
³ IC-MedTech Co., San Diego, CA, USA.
⁴ Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan; Group of Quantum-state Controlled MRI, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan.
⁵ Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan.

Abstract

Our graphical review expands the analysis of cancer vulnerabilities for high dose vitamin C, based on several facts, illustrating the cytotoxic potential of the ascorbate free radical (AFR) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH:cytochrome b5 oxidoreductase 3 (Cyb5R3). We propose that vitamin C can function in "protective mode" or "destructive mode" affecting cellular homeostasis, depending on the intracellular "steady-state" concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells. Thus, a specific anti-cancer effect can be achieved at high doses of vitamin C therapy. The review is intended for a wide audience of readers - from students to specialists in the field.

Keywords: Ascorbate free radical; Cancer; Mitochondria; NADH:Cytochrome b5 oxidoreductase 3; Redox signaling.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Ascorbic Acid / adverse effects*
Ascorbic Acid / chemistry
Ascorbic Acid / therapeutic use
Biomarkers, Tumor / metabolism
Chemotherapy, Adjuvant
Cytochrome-B(5) Reductase / metabolism
Free Radicals / metabolism*
Homeostasis / drug effects
Humans
Neoplasms / drug therapy*
Neoplasms / metabolism

Substances

Biomarkers, Tumor
Free Radicals
CYB5R3 protein, human
Cytochrome-B(5) Reductase
Ascorbic Acid