Ascorbate (Vitamin C) accelerates hydrogen-peroxide induced cell death in SK23 melanoma cells: vitamin C modulates the immune system?
Year: 2008
Session type: Poster / e-Poster / Silent Theatre session
RAFT Institute, Middlesex, UK
Abstract
Recent studies suggest that ascorbate (vitamin C) be re-evaluated in cancer treatment since intravenous, but not oral administration produces millimolar plasma ascorbate concentrations, relatively toxic to cancer compared to normal fibroblast cell lines in vitro (to 20 mM concentration) [1]. We, and others [2], have observed that ascorbate enhances hydrogen peroxide (H2O2) induced oxidative 8-oxo-dG DNA damage, and dehydroascorbate enhances H2O2 killing of Jurkat cells [3]. Selective drug activation in cancer cells to enhance H2O2 may prove to have chemotherapeutic potential. H2O2 however, is a normal product of the respiratory burst of activated neutrophils, likely present in the inflammatory infiltrate of tumours. H2O2 may also be elevated in cancer cells if catalase (normally detoxifying H2O2) is deficient. It was hypothesised that since oxidative DNA damage is accelerated by H2O2 /ascorbate, one of the functions of ascorbate is to enable H2O2-induced cell killing during the activation of the immune system.
Here we investigated the effects of ascorbate on H2O2-induced melanoma cell death in a system where metal-ions are chelated, and using ascorbate and dehydroascorbate to raise intracellular but not extracelluar ascorbate. Melanoma is radioresistant and less responsive to chemo- and immunotherapies than other cancers. We find both intracellular ascorbate and dehydroascorbate (20 mM) statistically increase the rate of melanoma cell killing (measured using a propidium iodide assay) via oxidative stress and 8-oxo-dG induction, at 10 and 1 mM H2O2.
These preliminary findings support the hypothesis that ascorbate accelerates cancer cell killing by H2O2 produced by activated neutrophils of the immune system.
References
[1] Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M.
Proc Natl Acad Sci 2005, 102, 13604-9.
[2] Riviere J, Ravanat J-L, Wagner JR. Free Rad Biol Med 2006, 2071-2079.
[3] Sané AT, Cantin AM, Paquette B, Wagner JR Cancer Chemother Pharmacol 2004, 54,315-21.
Recent studies suggest that ascorbate (vitamin C) be re-evaluated in cancer treatment since intravenous, but not oral administration produces millimolar plasma ascorbate concentrations, relatively toxic to cancer compared to normal fibroblast cell lines in vitro (to 20 mM concentration) [1]. We, and others [2], have observed that ascorbate enhances hydrogen peroxide (H2O2) induced oxidative 8-oxo-dG DNA damage, and dehydroascorbate enhances H2O2 killing of Jurkat cells [3]. Selective drug activation in cancer cells to enhance H2O2 may prove to have chemotherapeutic potential. H2O2 however, is a normal product of the respiratory burst of activated neutrophils, likely present in the inflammatory infiltrate of tumours. H2O2 may also be elevated in cancer cells if catalase (normally detoxifying H2O2) is deficient. It was hypothesised that since oxidative DNA damage is accelerated by H2O2 /ascorbate, one of the functions of ascorbate is to enable H2O2-induced cell killing during the activation of the immune system.
Here we investigated the effects of ascorbate on H2O2-induced melanoma cell death in a system where metal-ions are chelated, and using ascorbate and dehydroascorbate to raise intracellular but not extracelluar ascorbate. Melanoma is radioresistant and less responsive to chemo- and immunotherapies than other cancers. We find both intracellular ascorbate and dehydroascorbate (20 mM) statistically increase the rate of melanoma cell killing (measured using a propidium iodide assay) via oxidative stress and 8-oxo-dG induction, at 10 and 1 mM H2O2.
These preliminary findings support the hypothesis that ascorbate accelerates cancer cell killing by H2O2 produced by activated neutrophils of the immune system.
References
[1] Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M.
Proc Natl Acad Sci 2005, 102, 13604-9.
[2] Riviere J, Ravanat J-L, Wagner JR. Free Rad Biol Med 2006, 2071-2079.
[3] Sané AT, Cantin AM, Paquette B, Wagner JR Cancer Chemother Pharmacol 2004, 54,315-21.
