Free Radical Biology and Medicine ( IF 7.1 ) Pub Date : 2020-06-06 , DOI: 10.1016/j.freeradbiomed.2020.05.023 Dieanira T Erudaitius 1 , Garry R Buettner 2 , Victor G J Rodgers 1
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, , to describe the catalase activity in the presence of high levels of eH2O2. A simplified relationship emerges, when where and are the experimentally determined peroxisome permeability, average peroxisome radius, and the pseudo first-order reaction rate constant, respectively. is the catalase concentration in the peroxisome and . 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.
中文翻译:
在高浓度 H2O2 存在下,过氧化物酶体过氧化氢酶在胰腺和胶质母细胞瘤癌细胞系的有效性因子方面的潜伏期:对在癌症治疗中使用药理学抗坏血酸的影响。
先前的研究已经确定癌细胞系对高水平细胞外 H 2 O 2 (eH 2 O 2 ) 暴露的反应变化。这直接有助于我们了解药理学抗坏血酸 (P-AscH - ) 疗法的细胞功效。在这里,我们研究了导致细胞过氧化物酶体过氧化氢酶延迟的因素以及延迟在评估细胞暴露于 eH 2 O 2 中的重要性。首先,我们根据有效性因子为过氧化氢酶的延迟开发了一个数学框架,,描述在高水平 eH 2 O 2存在下的过氧化氢酶活性。一个简化的关系出现, 当 哪里 和 分别是实验确定的过氧化物酶体渗透性、平均过氧化物酶体半径和伪一级反应速率常数。 是过氧化物酶体中的过氧化氢酶浓度和 . 接下来,使用先前公布的参数来确定细胞系的潜伏效应:正常胰腺细胞 (H6c7)、胰腺癌细胞 (MIA PaCa-2) 和胶质母细胞瘤细胞 (LN-229、T98G 和 U-87),所有这些对暴露于高 eH 2 O 2的敏感性各不相同。结果表明,除了最易感的 MIA PaCa-2 细胞系外,有效性没有显着差异,与所有其他细胞系相比,该细胞系更高。这一结果是违反直觉的,并进一步暗示,作为一个单一参数的潜伏期在预测细胞系对 P-AscH 的易感性方面是无效的-治疗等效 eH 2O.因此,进一步的研究仍然是必要的,以确定为什么癌细胞的敏感性变化到P-阿希-治疗。