Cargando…

Anti-angiogenic effect of high doses of ascorbic acid

Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of t...

Descripción completa

Detalles Bibliográficos
Autores principales: Mikirova, Nina A, Ichim, Thomas E, Riordan, Neil H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562367/
https://www.ncbi.nlm.nih.gov/pubmed/18789157
http://dx.doi.org/10.1186/1479-5876-6-50
_version_ 1782159741128015872
author Mikirova, Nina A
Ichim, Thomas E
Riordan, Neil H
author_facet Mikirova, Nina A
Ichim, Thomas E
Riordan, Neil H
author_sort Mikirova, Nina A
collection PubMed
description Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA.
format Text
id pubmed-2562367
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-25623672008-10-07 Anti-angiogenic effect of high doses of ascorbic acid Mikirova, Nina A Ichim, Thomas E Riordan, Neil H J Transl Med Research Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA. BioMed Central 2008-09-12 /pmc/articles/PMC2562367/ /pubmed/18789157 http://dx.doi.org/10.1186/1479-5876-6-50 Text en Copyright © 2008 Mikirova et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Mikirova, Nina A
Ichim, Thomas E
Riordan, Neil H
Anti-angiogenic effect of high doses of ascorbic acid
title Anti-angiogenic effect of high doses of ascorbic acid
title_full Anti-angiogenic effect of high doses of ascorbic acid
title_fullStr Anti-angiogenic effect of high doses of ascorbic acid
title_full_unstemmed Anti-angiogenic effect of high doses of ascorbic acid
title_short Anti-angiogenic effect of high doses of ascorbic acid
title_sort anti-angiogenic effect of high doses of ascorbic acid
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562367/
https://www.ncbi.nlm.nih.gov/pubmed/18789157
http://dx.doi.org/10.1186/1479-5876-6-50
work_keys_str_mv AT mikirovaninaa antiangiogeniceffectofhighdosesofascorbicacid
AT ichimthomase antiangiogeniceffectofhighdosesofascorbicacid
AT riordanneilh antiangiogeniceffectofhighdosesofascorbicacid