2013
DOI: 10.3109/10715762.2012.755263
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Inhibitors of hydroperoxide metabolism enhance ascorbate-induced cytotoxicity

Abstract: Pharmacological ascorbate, via its oxidation, has been proposed as a pro-drug for the delivery of H2O2 to tumors. Pharmacological ascorbate decreases clonogenic survival of pancreatic cancer cells, which can be reversed by treatment with scavengers of H2O2. The goal of this study was to determine if inhibitors of intracellular hydroperoxide detoxification could enhance the cytotoxic effects of ascorbate. Human pancreatic cancer cells were treated with ascorbate alone or in combination with inhibitors of hydrop… Show more

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Cited by 58 publications
(77 citation statements)
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“…Gilloteaux et al 2014;Gilloteaux et al 2005;Herst et al 2012;Ma et al 2014;Martinotti et al 2011;Monti et al 2012;Ohtani et al 2007;Philips et al 2009;Verrax et al 2011;Welsh et al 2013). Some other studies took the strategy to facilitate peroxide formation by combing ascorbate with metal-based catalyst (Evans et al 2014;Kelley et al 1997;Rawal et al 2013), or inhibitors of peroxide metabolism (Olney et al 2013).…”
Section: Page 14 Of 30mentioning
confidence: 96%
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“…Gilloteaux et al 2014;Gilloteaux et al 2005;Herst et al 2012;Ma et al 2014;Martinotti et al 2011;Monti et al 2012;Ohtani et al 2007;Philips et al 2009;Verrax et al 2011;Welsh et al 2013). Some other studies took the strategy to facilitate peroxide formation by combing ascorbate with metal-based catalyst (Evans et al 2014;Kelley et al 1997;Rawal et al 2013), or inhibitors of peroxide metabolism (Olney et al 2013).…”
Section: Page 14 Of 30mentioning
confidence: 96%
“…2). In contrast to oral ascorbate, IV administration of ascorbate, at large doses, was similar to drug administration, producing concentrations that could be 100 fold or higher than maximally tolerated oral doses, and the peak could last for hours in millimolar range (Padayatty and Levine 2000;Padayatty et al 2004). …”
Section: Two Ice-breaking Discoveries That Reopened the Casementioning
confidence: 97%
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“…"Observational reports described ascorbate, given in pharmacologic doses of 10 g daily, as effective in treating some cancers and in improving patient well-being" [2] (Figure 1 [3] [4]). Ongoing research continues to improve the effectiveness of AA in killing cancer cells [5]. Subsequently, the same dose had no effect on patient well-being and survival in two double-blind placebo-controlled trials, and AA was discarded as a treatment modality [6] [7].…”
Section: Introductionmentioning
confidence: 99%