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Title: The latency of peroxisomal catalase in terms of effectiveness factor for pancreatic and glioblastoma cancer cell lines in the presence of high concentrations of H2O2: Implications for the use of pharmacological ascorbate in cancer therapy.

Authors: Erudaitius, Dieanira T; Buettner, Garry R; Rodgers, Victor G J

Published In Free Radic Biol Med, (2020 08 20)

Abstract: Previous research has identified variation in cancer cell line response to high levels of extracellular H2O2 (eH2O2) 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 eH2O2. First, we develop a mathematical framework for the latency of catalase in terms of an effectiveness factor, ηeff, to describe the catalase activity in the presence of high levels of eH2O2. A simplified relationship emerges, [Formula: see text] when mprp/Dij≪1, where mp,rp, 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 k2=1.7x107M-1s-1. 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 eH2O2. 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 eH2O. Thus, further research remains necessary to identify why cancer cells vary in susceptibility to P-AscH- therapy.

PubMed ID: 32522584 Exiting the NIEHS site

MeSH Terms: Antineoplastic Agents*/therapeutic use; Catalase; Cell Line; Cell Line, Tumor; Glioblastoma*/drug therapy; Humans; Hydrogen Peroxide; Pancreatic Neoplasms*/drug therapy

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