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Special Issue Editor

Dr. Gabi Dachs

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Guest Editor

Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand
Interests: ascorbate; cancer therapy; tumour hypoxia; hypoxia-inducible factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Robust clinical evidence for the efficacy of high dose vitamin C (ascorbate) for cancer treatment remains elusive. However, due to an improved understanding of the mechanism/s of action of ascorbate and encouraging data from small intervention trials, there is increasing interest in this vitamin.

To date, there are no confirmatory randomised controlled clinical trials on high dose ascorbate infusions in patients with cancer, in part due to the fact that there are still numerous outstanding questions. In particular, it is clear that ascorbate treatment is not effective in all patients, but that it modifies numerous vital molecular pathways, and may selectively eradicate cancer cells. It remains unclear who may benefit, what doses are required and how often, which molecular mechanisms are most important and how ascorbate interacts with other treatments.

This Antioxidants Special Issue aims to collect and publish studies aimed at answering some of these remaining questions and to provide an unbiased source of scientific information. We invite original research reports, and will consider reviews, meta-analyses and scientific hypotheses. Submissions of negative or controversial findings from robust scientific studies are also encouraged. We are interested in quantitative, biochemical and molecular analyses of cells in culture, in relevant animal models (knock-out mice, guinea pigs, zebrafish), in clinical samples and from patient studies.

Antioxidants are an open access scientific journal with a new Impact Factor (2020) of 5.014. An Article Processing Charge (APC) of 2000 CHF applies to papers accepted after peer review.

Dr. Gabi Dachs
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

enzyme cofactor
molecular pathways
antioxidant and pro-oxidant activity
cancer types
immune cells
tumour microenvironment
clinical trials

Published Papers (2 papers)

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Research

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17 pages, 1207 KiB

Open AccessArticle

Gene and Protein Expression Is Altered by Ascorbate Availability in Murine Macrophages Cultured under Tumour-Like Conditions

by Abel D. Ang, Margreet C. M. Vissers, Eleanor R. Burgess, Margaret J. Currie and Gabi U. Dachs

Antioxidants 2021, 10(3), 430; https://doi.org/10.3390/antiox10030430 - 11 Mar 2021

Cited by 1 | Viewed by 2351

Abstract

Tumour-associated macrophages (TAMs) are ubiquitously present in tumours and commonly associated with poor prognosis. In immune cells, ascorbate affects epigenetic regulation, differentiation and phenotype via its co-factor activity for the 2-oxoglutarate dependent dioxygenase enzymes. Here, we determined the effect of ascorbate on TAM development in response to tumour microenvironmental cues. Naïve murine bone marrow monocytes were cultured with Lewis Lung Carcinoma conditioned media (LLCM) or macrophage colony-stimulating factor (MCSF) to encourage the development into tumour-associated macrophages. Cells were stimulated with hypoxia (1% O₂), with or without ascorbate (500 µM) supplementation. Cells and media were harvested for gene, cell surface marker and protein analyses. LLCM supported bone marrow monocyte growth with >90% of cells staining CD11b⁺F4/80⁺, indicative of monocytes/macrophages. LLCM-grown cells showed increased expression of M2-like and TAM genes compared to MCSF-grown cells, which further increased with hypoxia. In LLCM-grown cells, ascorbate supplementation was associated with increased F4/80 cell surface expression, and altered gene expression and protein secretion. Our study shows that ascorbate modifies monocyte phenotype when grown under tumour microenvironmental conditions, but this was not clearly associated with either a pro- or anti-tumour phenotype, and reflects a complex and nuanced response of macrophages to ascorbate. Overall, ascorbate supplementation clearly has molecular consequences for TAMs, but functional and clinical consequences remain unknown. Full article

(This article belongs to the Special Issue Vitamin C in Cancer: From Mechanistic Insights to Clinical Intervention Trials)

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Review

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15 pages, 1097 KiB

Open AccessReview

The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review

by Marcelo Villagran, Jorge Ferreira, Miquel Martorell and Lorena Mardones

Antioxidants 2021, 10(12), 1894; https://doi.org/10.3390/antiox10121894 - 26 Nov 2021

Cited by 27 | Viewed by 6570

Abstract

Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and transport of vitamin C into cancer cells. The reviewed studies show that vitamin C intake from natural sources can prevent the development of pulmonary and breast cancer, and that vitamin C synergizes with gemcitabine and erlotinib in pancreatic cancer. In vitro assays reveal that vitamin C synergizes with DNA-methyl transferase inhibitors. However, vitamin C was not associated with cancer prevention in a Mendelian randomized study. In conclusion, the role of vitamin C in the prevention and treatment of cancer is still an ongoing area of research. It is necessary that new phase II and III clinical trials be performed to collect stronger evidence of the therapeutic role of vitamin C in cancer. Full article

(This article belongs to the Special Issue Vitamin C in Cancer: From Mechanistic Insights to Clinical Intervention Trials)

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