Proteomic analysis reveals upregulation of RKIP in S‐180 implanted BALB/C mouse after treatment with ascorbic acid

Park, Sung Yong; Ahn, Eun Sook; Lee, Sukchan; Jung, Manyong; Park, Jin Hee; Yi, Sang Yeop; Yeom, Chang‐Hwan

doi:10.1002/jcb.22097

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…Pharmacologic ascorbate treatment (1.5 g/kg injected intraperitoneally) upregulated hepatic expression of rapidly accelerated fibrosarcoma (Raf) kinase inhibitory protein (RKIP) and annexin A5 in a S-180 sarcoma xenograft model, coincident with decreased tumor growth and increased survival rate relative to controls (61). Messenger RNA (mRNA) levels were also upregulated, suggesting a transcriptional control mechanism.…”

Section: A Role For Transcription Factors and Signal Transduction Patmentioning

confidence: 99%

Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics

Parrow

Leshin

Levine

2013

Antioxidants & Redox Signaling

110

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Significance: Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. However, the route of administration results in major differences in ascorbate bioavailability. Tissue and plasma concentrations are tightly controlled in response to oral administration, but this can be bypassed by intravenous administration. These data provide a plausible scientific rationale for the absence of a response to orally administered ascorbate in the Mayo clinic trials and indicate the need to reassess ascorbate as a cancer therapeutic. Recent Advances: High dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide (H 2 O 2 ). Murine xenograft models confirm a growth inhibitory effect of pharmacological concentrations. The safety of intravenous ascorbate has been verified in encouraging pilot clinical studies. Critical Issues: Neither the selective toxicity of pharmacologic ascorbate against cancer cells nor the mechanism of H 2 O 2 -mediated cytotoxicity is fully understood. Despite promising preclinical data, the question of clinical efficacy remains. Future Directions: A full delineation of mechanism is of interest because it may indicate susceptible cancer types. Effects of pharmacologic ascorbate used in combination with standard treatments need to be defined. Most importantly, the clinical efficacy of ascorbate needs to be reassessed using proper dosing, route of administration, and controls.

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Section: A Role For Transcription Factors and Signal Transduction Patmentioning

confidence: 99%

Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics

Parrow

Leshin

Levine

2013

Antioxidants & Redox Signaling

110

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“…In vivo and in vitro studies have shown that some of the effects associated with AA are at transcriptional level (Park et al 2009; Shin et al 2004; Belin et al 2009). Despite a number of solid indications, the mechanism by which ascorbic acid affects gene expression is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects

Canali¹,

Natarelli²,

Leoni³

et al. 2014

Genes Nutr

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In order to study the effects of vitamin C supplementation on gene expression and compare its action between physiological and inflammatory conditions, a pilot study was set up utilizing microarray and qPCR technologies. Five healthy volunteers were supplemented with 1 g vitamin C (Redoxon®) per day for five consecutive days. Peripheral blood mononuclear cells (PBMNC) were isolated before and just after the last supplementation, and RNA was isolated for the Affymetrix gene 1.0 ST chip analysis. PBMNC were also, ex vivo, treated with LPS, and gene expression was quantified by means of a “Human NFkB Signaling” qPCR array. Only a very moderate effect on the baseline gene expression modulation was associated with vitamin C supplementation. However, in spite of the limited number of subjects analyzed, vitamin C supplementation resulted in a markedly different modulation of gene expression upon the inflammatory stimulus, specifically at the level of the MyD88-dependent pathway and of the anti-inflammatory cytokine IL-10 synthesis. This study suggests that vitamin C supplementation in healthy subjects, not selected according to a specific genetic profile, consuming an adequate amount of vitamin C, and having a satisfactory vitamin C plasma concentration at the baseline, does not result in a significant modification of gene expression profile. Under this satisfactory micronutrient status, supplementation of vitamin C is “buffered” within a homeostatic physiological equilibrium. Differently, following a second “hit” constituted of an inflammatory stimulus such as LPS, able to trigger a critical burst to the normal physiological state, the higher availability of ascorbic acid emerges, and results in a significant modulation of cell response.

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“…K alone exhibited an inhibitory effect only at the highest concentration tested and following 48 Another potential explanation for the heterogeneous effect observed in different breast cancer cell lines upon treatment with A and K in the present study may be the cell length and conformation of telomeres, which may be affected by the concentration of K + in the different cell lines tested (61). In healthy cells, each cell replication results in 50-200 bp loss of the telomere (62).…”

Section: Discussionmentioning

confidence: 59%

“…A possesses both pro-oxidant and anti-oxidant properties (42)(43)(44)(45)(46)(47)(48)(49)(50). Although the preventive anti-cancer effect of A results from its anti-oxidant properties (42), previous in vitro studies and mouse models have demonstrated that A is able to inhibit cell proliferation in various types of cancer due to its ability to induce the production of H 2 O 2 (43-49) without being toxic to non-cancerous cells (43,50).…”

Section: Discussionmentioning

confidence: 99%

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

et al. 2016

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Abstract.Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

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Proteomic analysis reveals upregulation of RKIP in S‐180 implanted BALB/C mouse after treatment with ascorbic acid

Cited by 17 publications

References 36 publications

Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics

Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics

Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

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