Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07

AUTHORS

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

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 (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS-induced cell death for their anti-tumor properties. More... »

PAGES

27439

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep27439

DOI

http://dx.doi.org/10.1038/srep27439

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051751166

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27278439


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