Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation

Milardi, Domenico; Pelosi, Elvira; Castelli, Germana; Lo‐Coco, Francesco; Testa, Ugo

doi:10.1016/j.bcmd.2017.09.005

Cited by 65 publications

(53 citation statements)

References 91 publications

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“…Vitamin C (VC) plays important roles in many different biological processes, spanning from stem cell differentiation to cancer cell biology. 1,2 VC is a potent antioxidant and free radical scavenger, as well as an essential cofactor in many enzymatic reactions. Moreover, VC has recently been found to selectively kill colorectal cancer cells with KRAS or BRAF mutations.…”

Section: Introductionmentioning

confidence: 99%

Vitamin C promotes the proliferation and effector functions of human γδ T cells

Kouakanou

Peters

et al. 2019

Cell Mol Immunol

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γδ T cells are of interest as effector cells for cellular immunotherapy due to their HLA-non-restricted lysis of many different tumor cell types. Potential applications include the adoptive transfer of in vitro-expanded γδ T cells. Therefore, it is important to optimize the culture conditions to enable maximal proliferative and functional activity. Vitamin C (L-ascorbic acid) is an essential vitamin with multiple effects on immune cells. It is a cofactor for several enzymes, has antioxidant activity, and is an epigenetic modifier. Here, we investigated the effects of vitamin C (VC) and its more stable derivative, L-ascorbic acid 2-phosphate (pVC), on the proliferation and effector function of human γδ T cells stimulated with zoledronate (ZOL) or synthetic phosphoantigens (pAgs). VC and pVC did not increase γδ T-cell expansion within ZOL-or pAg-stimulated PBMCs, but increased the proliferation of purified γδ T cells and 14-day-expanded γδ T-cell lines in response to γδ T-cell-specific pAgs. VC reduced the apoptosis of γδ T cells during primary stimulation. While pVC did not prevent activation-induced death of pAg-restimulated γδ T cells, it enhanced the cell cycle progression and cellular expansion. Furthermore, VC and pVC enhanced cytokine production during primary activation, as well as upon pAg restimulation of 14-day-expanded γδ T cells. VC and pVC also increased the oxidative respiration and glycolysis of γδ T cells, but stimulus-dependent differences were observed. The modulatory activity of VC and pVC might help to increase the efficacy of γδ T-cell expansion for adoptive immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Vitamin C promotes the proliferation and effector functions of human γδ T cells

Kouakanou

Peters

et al. 2019

Cell Mol Immunol

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“…Anticancer properties of vitamin C have been reviewed in several recent papers (e.g., [4,[6][7][8][9][10]). These studies suggest several potential targets of anticancer action of vitamin C-some of them will be described and referenced in the next sections.…”

Section: Introductionmentioning

confidence: 99%

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations

Pawłowska

Szczepańska

Błasiak

2019

Oxidative Medicine and Cellular Longevity

102

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Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation. Dietary vitamin C from natural sources is taken with other compounds affecting its bioavailability and biological effects. High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells. An oxidized form of vitamin C, dehydroascorbate, is transported through glucose transporters, and cancer cells switch from oxidative phosphorylation to glycolysis in energy production so an excess of vitamin C may limit glucose transport and ATP production resulting in energetic crisis and cell death. Vitamin C may change the metabolomic and epigenetic profiles of cancer cells, and activation of ten-eleven translocation (TET) proteins and downregulation of pluripotency factors by the vitamin may eradicate cancer stem cells. Metastasis, the main reason of cancer-related deaths, requires breakage of anatomical barriers containing collagen, whose synthesis is promoted by vitamin C. Vitamin C induces degradation of hypoxia-inducible factor, HIF-1, essential for the survival of tumor cells in hypoxic conditions. Dietary vitamin C may stimulate the immune system through activation of NK and T cells and monocytes. Pharmacological doses of vitamin C may inhibit cancer transformation in several pathways, but further studies are needed to address both mechanistic and clinical aspects of this effect.

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“…Moreover, vitamin C as an antioxidant and a free radical scavenger serves as an essential cofactor for many enzymatic reactions through iron-, copperand 2-oxoglutarate-dependent dioxygenases. In addition, AA was found to be a cofactor for methyl cytosine dioxygenases that are responsible for DNA demethylation and a possible cofactor for some JmjC domain-containing histone demethylases involved in histone demethylation [24][25][26][27][28][29][30]. Laboratory experiments evidenced that L-ascorbic acid has a double-faced nature.…”

Section: Introductionmentioning

confidence: 99%

Using an <i>Escherichia Coli</i> K-12/<i>recA-gfpmut2</i> Microbial Biosensor to Assess the Impact of Cyclophosphamide and L-ascorbic Acid Residues on Living Bacteria Cells

Matejczyk¹,

Świsłocka²,

Lewandowski³

2020

Pol. J. Environ. Stud.

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Pharmaceutical residues and their transformation products (TPs) have been found in wastewaters and aquatic environments, and they cause adverse effects in aquatic organisms, especially upon chronic exposure and even at very low doses. Cyclophosphamide (CP) is a common alkylating agent that is effective against a wide variety of tumors. L-ascorbic acid is a known water-soluble vitamin that has antioxidant properties. The pharmaceutical residues of both drugs are detected in the environment, and as biologically active molecules they have the ability to affect organisms. In this work we presented the use of a microbiological biosensor E. coli K-12/recA-gfpmut2 in the assessment of the effects of residues of cyclophosphamide and vitamin C and their mixtures on living cells. In our studies, we have shown that mixtures of CP and vitamin C in the highest CP concentrations are more toxic to E. coli strain compared to parent chemicals. In addition, we also found that drug mixtures, especially at the highest CP concentrations, more strongly stimulate the recA promoter and gfp gene expression. We showed that an Escherichia coli K-12/recA-gfpmut2 microbial biosensor is a useful tool in assessing the impact of pharmaceutical residues of cyclophosphamide and L-ascorbic acid and their mixture on living bacteria cells. A stronger impact and toxicity of the mixtures of both tested chemical compounds was found in comparison to parent chemicals.

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Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation

Cited by 65 publications

References 91 publications

Vitamin C promotes the proliferation and effector functions of human γδ T cells

Vitamin C promotes the proliferation and effector functions of human γδ T cells

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations

Using an <i>Escherichia Coli</i> K-12/<i>recA-gfpmut2</i> Microbial Biosensor to Assess the Impact of Cyclophosphamide and L-ascorbic Acid Residues on Living Bacteria Cells

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