Ascorbate as a bioactive compound in cancer therapy: the old classic strikes back
Author
dc.contributor.author
González Montero, Jaime
Author
dc.contributor.author
Chichiarelli, Silvia
Author
dc.contributor.author
Eufemi, Margherita
Author
dc.contributor.author
Altieri, Fabio
Author
dc.contributor.author
Saso, Luciano
Author
dc.contributor.author
Rodrigo Salinas, Ramón
Admission date
dc.date.accessioned
2022-07-18T16:39:22Z
Available date
dc.date.available
2022-07-18T16:39:22Z
Publication date
dc.date.issued
2022
Cita de ítem
dc.identifier.citation
Molecules 2022, 27, 3818
es_ES
Identifier
dc.identifier.other
10.3390/molecules27123818
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/186797
Abstract
dc.description.abstract
Cancer is a disease of high mortality, and its prevalence has increased steadily in the last few years. However, during the last decade, the development of modern chemotherapy schemes, new radiotherapy techniques, targeted therapies and immunotherapy has brought new hope in the treatment of these diseases. Unfortunately, cancer therapies are also associated with frequent and, sometimes, severe adverse events. Ascorbate (ascorbic acid or vitamin C) is a potent water-soluble antioxidant that is produced in most mammals but is not synthesised endogenously in humans, which lack enzymes for its synthesis. Ascorbate has antioxidant effects that correspond closely to the dose administered. Interestingly, this natural antioxidant induces oxidative stress when given intravenously at a high dose, a paradoxical effect due to its interactions with iron. Importantly, this deleterious property of ascorbate can result in increased cell death. Although, historically, ascorbate has been reported to exhibit anti-tumour properties, this effect has been questioned due to the lack of available mechanistic detail. Recently, new evidence has emerged implicating ferroptosis in several types of oxidative stress-mediated cell death, such as those associated with ischemia-reperfusion. This effect could be positively modulated by the interaction of iron and high ascorbate dosing, particularly in cell systems having a high mitotic index. In addition, it has been reported that ascorbate may behave as an adjuvant of favourable anti-tumour effects in cancer therapies such as radiotherapy, radio-chemotherapy, chemotherapy, immunotherapy, or even in monotherapy, as it facilitates tumour cell death through the generation of reactive oxygen species and ferroptosis. In this review, we provide evidence supporting the view that ascorbate should be revisited to develop novel, safe strategies in the treatment of cancer to achieve their application in human medicine.
es_ES
Lenguage
dc.language.iso
en
es_ES
Publisher
dc.publisher
MDPI
es_ES
Type of license
dc.rights
Attribution-NonCommercial-NoDerivs 3.0 United States