2008
DOI: 10.1073/pnas.0804226105
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Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice

Abstract: Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogenperoxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Real-time microdialysis sampling in mice bearing glioblastoma xenografts showed that a single pharmacologi… Show more

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Cited by 730 publications
(862 citation statements)
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“…However, infected patients often have bacteria in their interstitial fluid, too. It is in interstitial fluid that the concentrations of ascorbate and hydrogen peroxide rise most after parenteral administration of an extremely high dose of ascorbate (4000 mg/kg) (10). Perhaps the same increase in interstitial fluid hydrogen peroxide concentration may be achieved with lower ascorbate doses in septic patients because of an abundance of redox-reactive transition metals that may generate hydrogen peroxide through oxidation of ascorbate.…”
Section: Bacterial Replicationmentioning
confidence: 85%
See 1 more Smart Citation
“…However, infected patients often have bacteria in their interstitial fluid, too. It is in interstitial fluid that the concentrations of ascorbate and hydrogen peroxide rise most after parenteral administration of an extremely high dose of ascorbate (4000 mg/kg) (10). Perhaps the same increase in interstitial fluid hydrogen peroxide concentration may be achieved with lower ascorbate doses in septic patients because of an abundance of redox-reactive transition metals that may generate hydrogen peroxide through oxidation of ascorbate.…”
Section: Bacterial Replicationmentioning
confidence: 85%
“…One basis for this concern is that ascorbate reduces the valence of free transition metals, such as iron (e.g., ascorbate reduces FeIII to FeII), which then catalyze the formation of hydrogen peroxide. Hydrogen peroxide is generated in the interstitial fluid by oxidation of large amounts of exogenous ascorbate (10) and this may alter the function of some cells. Another source of hydrogen peroxide is extravasated neutrophils, because ascorbate enhances reactive oxygen species production by neutrophils exposed to E. coli (52).…”
Section: Vitamin C Dosage and Safetymentioning
confidence: 99%
“…I n this issue of PNAS, Chen et al (1) show that i.p. injection of ''pharmacologic doses'' of vitamin C decreases the growth and weight of human, rat, and murine tumor xenografts in athymic, nude mice.…”
mentioning
confidence: 99%
“…Furthermore, in our study, precautions were taken to minimize endogenous production of ROS by making cell's incubation at low temperature and empirically during 18H. On other hand, the oxidative effect of ascorbate is proposed essentially as a safe medical alternative to treat cancer but only at high plasmatic doses which cannot be obtained except by intravenous infusion (IV) (Chen et al, 2008). Meanwhile, a large amount (mM) of ascorbate would be interacting with RBC.…”
Section: Discussionmentioning
confidence: 99%
“…6). Chen et al (2008;2007;2005) suggested that ascorbate, at pharmacological concentrations, is a pro-drug for H 2 O 2 delivery to tissues with major therapeutic implications. However, such conclusions may be criticized viewing the limits of the experimental model and don't concord with our data that showed that AA alone (model 0) has a low impact on the first oxidative pathway compared to PFEM+Cu ++ and PFEM+H 2 O 2 +Cu ++ .…”
Section: Discussionmentioning
confidence: 99%