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Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects by Hamid R. Molavian; Aaron Goldman; Colin J. Phipps; Mohammad Kohandel; Bradly G. Wouters; Shiladitya Sengupta; Sivabal Sivaloganathan is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using __in vitro__ assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H~2~O~2~), to induce cell death. Interestingly, we did not observe any correlation between intracellular H~2~O~2~ and cell survival, suggesting that cell death by H~2~O~2~ is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H~2~O~2~. These findings provide a putative mechanistic explanation for t

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Author

Hamid R. Molavian; Aaron Goldman; Colin J. Phipps; Mohammad Kohandel; Bradly G. Wouters; Shiladitya Sengupta; Sivabal Sivaloganathan

Publisher

Springer Science and Business Media LLC

Published

2016

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)