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(−)] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH(−) can produce a high flux of H(2)O(2) in tumors. Catalase is the major enzyme for detoxifying high concentrations of H(2)O(2). We hypothesize that sensitivity of tumor cells to P-AscH(−) compared to normal cells is due to their lower capacity to metabolize H(2)O(2). Rate constants for removal of H(2)O(2) (k(cell)) 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 H(2)O(2) was revealed, with the average k(cell) for normal cells being twice that of tumor cells. The ED(50) (50% clonogenic survival) of P-AscH(−) correlated directly with k(cell) and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH(−).