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Review
. 2020 Dec 18;12(12):3869.
doi: 10.3390/nu12123869.

Vitamin C Transporters and Their Implications in Carcinogenesis

Kinga Linowiecka  1 , Marek Foksinski  2 , Anna A Brożyna  1
Affiliations
Review

Vitamin C Transporters and Their Implications in Carcinogenesis

Kinga Linowiecka et al. Nutrients. .

Abstract

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe2+ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs' polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.

Keywords: SVCT polymorphisms; carcinogenesis; vitamin C.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Vitamin C redox states. Ascorbic acid undergoes two reversible hydrogen dissociations to form ascorbate monoanions and ascorbate dianions, respectively. Then, ascorbate dianons can be subsequently subjected to one-electron oxidation to create ascorbate radicals. These are not highly reactive components; however, they can undergo another one-electron oxidation to form dehydroascorbic acid.
Figure 2
Figure 2
Vitamin C’s role in 2-oxoglutarate and Fe2+ dependent dioxygenase (2-OGDD) activity. Legend abbreviations: ASc—ascorbate; SCVT1—sodium dependent vitamin C transporter 1; SCVT2—sodium dependent vitamin C transporter 2; DHA—dehydroascorbic acid, TET—ten–eleven translocation proteins; JHDM—Jumonji C-domain-containing histone demethylases; HPH—hypoxia-inducible factor prolyl hydroxylases; FIH—factor-inhibiting hypoxia-inducible factor; HIF1α—subunit α of the hypoxia inducible factor 1; HIF2 α—subunit α of the hypoxia inducible factor 2. Ascorbate can be engaged in restoring the activity of 2-OGDD enzymes by reducing Fe3+ to Fe2+, which can be found in the catalytic center of those enzymes. 2-OGDD enzymes also require 2-oxoglutarate to maintain their catalytic activity. TET, JHDM, HPH and FIH are members of the 2-OGDD family, and their main roles in cell biochemistry are based on DNA demethylation (TET proteins), histone demethylation (JHDM proteins) and HIF1α and HIF2 α activation (HPH and FIH proteins). A more detailed description is given in the text.
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