Vitamin C as a Modulator of the Response to Cancer Therapy

Molecules

卷:24

Przemysław Kopczyński¹  Julia Masternak²  Błażej Rubiś²  Anatoly Zhitkovich³  Wojciech Barczak⁴  Wiktoria Blaszczak⁴ 

[1] Centre for Orthodontic Mini-implants at the Department and Clinic of Maxillofacial Orthopedics and Orthodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland;

[2] Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 60-355 Poznan, Poland;

[3] Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, USA;

[4] Radiobiology Lab, The Greater Poland Cancer Centre, Garbary, 61-866 Poznan, Poland;

关键词: vitamin C;    ascorbate;    cancer;    cancer therapy;    chemotherapy;    oxidative stress;    ROS;    hypoxia;   

DOI  :  10.3390/molecules24030453

来源: DOAJ

【 摘 要 】

Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5′-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.

【 授权许可】

Unknown