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• W1964546987 abstract "Ascorbic acid (AA) has been reported to inhibit tumor cell growth through the generation of extracellular hydrogen peroxide (H2O2). However, the clinical utility of AA has been limited by relatively low potency and in vivo efficacy. This study reports that the metalloporphyrin, Mn(III) tetrakis(N-methylpyridinium-2-yl)porphyrin5+ (MnTMPyP), has a potent synergistic cytotoxic effect when combined with AA in a variety of cancer cell lines. In the presence of MnTMPyP, the concentration of AA required to inhibit cancer cell growth was markedly reduced. In vitro (cell-free) experiments demonstrated that AA alone enhanced the Fenton reaction that produces cytotoxic hydroxyl radical (HO•); however, this reaction was limited by the low rate by which AA generates H2O2 (Fenton reaction substrate) from O2. MnTMPyP catalyzed H2O2 generation through the AA-facilitated Mn(II ⇔ III)TMPyP redox cycle and thereby markedly potentiated the Fenton reaction. Accordingly, MnTMPyP and AA resulted in increased cellular levels of H2O2 and HO• in cancer cells, which mediate the synergistic cytotoxicity of this combined treatment. This effect was inhibited by cellular enzymes that metabolize H2O2, such as catalase and glutathione peroxidase, suggesting that selective killing of cancer cells deficient in such enzymes can be achieved in vivo." @default.
• W1964546987 created "2016-06-24" @default.
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• W1964546987 date "2010-08-01" @default.
• W1964546987 modified "2023-09-26" @default.
• W1964546987 title "Metalloporphyrin Synergizes with Ascorbic Acid to Inhibit Cancer Cell Growth Through Fenton Chemistry" @default.
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• W1964546987 doi "https://doi.org/10.1089/cbr.2009.0756" @default.
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