Tumor cells have decreased ability to metabolize H 2 O 2 : Implications for pharmacological ascorbate in cancer therapy.

Ascorbate (AscH- ) functions as a versatile reducing agent. At pharmacological doses (P-AscH- ; [plasma AscH- ] ≥≈20mM), achievable through intravenous delivery, oxidation of P-AscH- can produce a high flux of H2 O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2 O2 . We hypothesize that sensitivity of tumor cells to P-AscH- compared to normal cells is due to their lower capacity to metabolize H2 O2 . Rate constants for removal of H2 O2 (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 H2 O2 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- .