The latency of peroxisomal catalase in terms of effectiveness factor for pancreatic and glioblastoma cancer cell lines in the presence of high concentrations of HO: Implications for the use of pharmacological ascorbate in cancer therapy.

Previous research has identified variation in cancer cell line response to high levels of extracellular HO (eHO) exposure. This directly contributes to our understanding cellular efficacy of pharmacological ascorbate (P-AscH) therapy. Here we investigate the factors contributing to latency of peroxisomal catalase of a cell and the importance of latency in evaluating cell exposure to eHO. First, we develop a mathematical framework for the latency of catalase in terms of an effectiveness factor, η, to describe the catalase activity in the presence of high levels of eHO. A simplified relationship emerges, [Formula: see text] when mr/D≪1, where m,r, and [Formula: see text] are the experimentally determined peroxisome permeability, average peroxisome radius, and the pseudo first-order reaction rate constant, respectively. [Formula: see text] is the catalase concentration in the peroxisome and k=1.7x10Ms. Next, previously published parameters are used to determine the latency effect of the cell lines: normal pancreatic cells (H6c7), pancreatic cancer cells (MIA PaCa-2), and glioblastoma cells (LN-229, T98G, and U-87), all which vary in their susceptibility to exposure to high eHO. The results show that effectiveness is not significantly different except for the most susceptible, MIA PaCa-2 cell line, which is higher when compared to all other cell lines. This result is counterintuitive and further implies that latency, as a single parameter, is ineffective in forecasting cell line susceptibility to P-AscH therapy equivalent eHO. Thus, further research remains necessary to identify why cancer cells vary in susceptibility to P-AscH therapy.