UC Riverside

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, η_eff, to describe the catalase activity in the presence of high levels of eH₂O₂. A simplified relationship emerges, [Formula: see text] when m_pr_p/D_ij≪1, where m_p,r_p, 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.