Vitamin C as a Modulator of the Response to Cancer Therapy
AbstractAscorbic 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. View Full-Text
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Blaszczak, W.; Barczak, W.; Masternak, J.; Kopczyński, P.; Zhitkovich, A.; Rubiś, B. Vitamin C as a Modulator of the Response to Cancer Therapy. Molecules 2019, 24, 453.
Blaszczak W, Barczak W, Masternak J, Kopczyński P, Zhitkovich A, Rubiś B. Vitamin C as a Modulator of the Response to Cancer Therapy. Molecules. 2019; 24(3):453.Chicago/Turabian Style
Blaszczak, Wiktoria; Barczak, Wojciech; Masternak, Julia; Kopczyński, Przemysław; Zhitkovich, Anatoly; Rubiś, Błażej. 2019. "Vitamin C as a Modulator of the Response to Cancer Therapy." Molecules 24, no. 3: 453.
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