Tumor cells have decreased ability to metabolize HO: 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 HO in tumors. Catalase is the major enzyme for detoxifying high concentrations of HO. We hypothesize that sensitivity of tumor cells to P-AscH compared to normal cells is due to their lower capacity to metabolize HO. Rate constants for removal of HO (k) 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 HO was revealed, with the average k for normal cells being twice that of tumor cells. The ED (50% clonogenic survival) of P-AscH correlated directly with k and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH.