Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects
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 mo...
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| Format: | Article |
| Language: | en_US |
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Springer Nature
2016
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| Online Access: | http://hdl.handle.net/1721.1/103862 |
| _version_ | 1826205111647469568 |
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| author | Molavian, Hamid R. Goldman, Aaron Phipps, Colin J. Kohandel, Mohammad Wouters, Bradly G. Sengupta, Shiladitya Sivaloganathan, Sivabal |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Molavian, Hamid R. Goldman, Aaron Phipps, Colin J. Kohandel, Mohammad Wouters, Bradly G. Sengupta, Shiladitya Sivaloganathan, Sivabal |
| author_sort | Molavian, Hamid R. |
| collection | MIT |
| description | 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[subscript 2]O[subscript 2]), to induce cell death. Interestingly, we did not observe any correlation between intracellular H[subscript 2]O[subscript 2] and cell survival, suggesting that cell death by H[subscript 2]O[subscript 2] is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H[subscript 2]O[subscript 2]. 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. |
| first_indexed | 2024-09-23T13:07:14Z |
| format | Article |
| id | mit-1721.1/103862 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:07:14Z |
| publishDate | 2016 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1038622022-10-01T13:11:56Z Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects Molavian, Hamid R. Goldman, Aaron Phipps, Colin J. Kohandel, Mohammad Wouters, Bradly G. Sengupta, Shiladitya Sivaloganathan, Sivabal Harvard University--MIT Division of Health Sciences and Technology Sengupta, Shiladitya 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[subscript 2]O[subscript 2]), to induce cell death. Interestingly, we did not observe any correlation between intracellular H[subscript 2]O[subscript 2] and cell survival, suggesting that cell death by H[subscript 2]O[subscript 2] is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H[subscript 2]O[subscript 2]. 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. Natural Sciences and Engineering Research Council of Canada (NSERC discovery grant) Natural Sciences and Engineering Research Council of Canada (NSERC/CIHR Collaborative Health Research grant) 2016-08-08T14:57:53Z 2016-08-08T14:57:53Z 2016-06 2015-10 Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/103862 Molavian, Hamid R., Aaron Goldman, Colin J. Phipps, Mohammad Kohandel, Bradly G. Wouters, Shiladitya Sengupta, and Sivabal Sivaloganathan. “Drug-Induced Reactive Oxygen Species (ROS) Rely on Cell Membrane Properties to Exert Anticancer Effects.” Scientific Reports 6 (June 9, 2016): 27439. en_US http://dx.doi.org/10.1038/srep27439 Scientific Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Scientific Reports |
| spellingShingle | Molavian, Hamid R. Goldman, Aaron Phipps, Colin J. Kohandel, Mohammad Wouters, Bradly G. Sengupta, Shiladitya Sivaloganathan, Sivabal Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects |
| title | Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects |
| title_full | Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects |
| title_fullStr | Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects |
| title_full_unstemmed | Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects |
| title_short | Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects |
| title_sort | drug induced reactive oxygen species ros rely on cell membrane properties to exert anticancer effects |
| url | http://hdl.handle.net/1721.1/103862 |
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