Limits...
Anti-angiogenic effect of high doses of ascorbic acid.

Mikirova NA, Ichim TE, Riordan NH - J Transl Med (2008)

Bottom Line: We hypothesized that AA may exert anti-angiogenic effects.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bio-Communications Research Institute, Wichita, Kansas, USA. nmikirova@brightspot.org

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Ascorbic acid attenuates tube formation in HUVECs, HUAECs and EPCs. Average data for three cell lines treated by different concentrations of AA during 3–6 hrs. Number of intact loops in wells treated by ascorbic acid was normalized on the number of intact loops in control wells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2562367&req=5

Figure 3: Ascorbic acid attenuates tube formation in HUVECs, HUAECs and EPCs. Average data for three cell lines treated by different concentrations of AA during 3–6 hrs. Number of intact loops in wells treated by ascorbic acid was normalized on the number of intact loops in control wells.

Mentions: The average data for all experiments conducted for all three cell lines are presented in Figure 3. Data used for Figure 3 were collected after 3–6 hours of culture medium exposure for both endothelial progenitor cells and mature endothelila cells to the varied AA concentrations used. Data were averaged for each concentration of AA, and the number of closed loops was normalized on the number of intact closed loops in control wells.


Anti-angiogenic effect of high doses of ascorbic acid.

Mikirova NA, Ichim TE, Riordan NH - J Transl Med (2008)

Ascorbic acid attenuates tube formation in HUVECs, HUAECs and EPCs. Average data for three cell lines treated by different concentrations of AA during 3–6 hrs. Number of intact loops in wells treated by ascorbic acid was normalized on the number of intact loops in control wells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2562367&req=5

Figure 3: Ascorbic acid attenuates tube formation in HUVECs, HUAECs and EPCs. Average data for three cell lines treated by different concentrations of AA during 3–6 hrs. Number of intact loops in wells treated by ascorbic acid was normalized on the number of intact loops in control wells.
Mentions: The average data for all experiments conducted for all three cell lines are presented in Figure 3. Data used for Figure 3 were collected after 3–6 hours of culture medium exposure for both endothelial progenitor cells and mature endothelila cells to the varied AA concentrations used. Data were averaged for each concentration of AA, and the number of closed loops was normalized on the number of intact closed loops in control wells.

Bottom Line: We hypothesized that AA may exert anti-angiogenic effects.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bio-Communications Research Institute, Wichita, Kansas, USA. nmikirova@brightspot.org

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus