Tumor cells have decreased ability to metabolize H₂O₂: 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 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 (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 H₂O₂ was revealed, with the average k_cell for normal cells being twice that of tumor cells. The ED₅₀ (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^-.