Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy

Abstract

Ascorbate (AscH−) functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell) and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival) of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−.