Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy
Ascorbate (AscH−) functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-12-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231716302634 |
| _version_ | 1828349058874343424 |
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| author | Claire M. Doskey Visarut Buranasudja Brett A. Wagner Justin G. Wilkes Juan Du Joseph J. Cullen Garry R. Buettner |
| author_facet | Claire M. Doskey Visarut Buranasudja Brett A. Wagner Justin G. Wilkes Juan Du Joseph J. Cullen Garry R. Buettner |
| author_sort | Claire M. Doskey |
| collection | DOAJ |
| description | Ascorbate (AscH−) functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell) and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival) of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−. |
| first_indexed | 2024-04-14T01:03:55Z |
| format | Article |
| id | doaj.art-03863663ae414bff9582358298e07027 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-14T01:03:55Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-03863663ae414bff9582358298e070272022-12-22T02:21:18ZengElsevierRedox Biology2213-23172016-12-0110C27428410.1016/j.redox.2016.10.010Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapyClaire M. Doskey0Visarut Buranasudja1Brett A. Wagner2Justin G. Wilkes3Juan Du4Joseph J. Cullen5Garry R. Buettner6Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USAInterdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USAFree Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USADepartment of Surgery, The University of Iowa, Iowa City, IA 52242, USADepartment of Surgery, The University of Iowa, Iowa City, IA 52242, USAFree Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USAInterdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USAAscorbate (AscH−) functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell) and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival) of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−.http://www.sciencedirect.com/science/article/pii/S2213231716302634 |
| spellingShingle | Claire M. Doskey Visarut Buranasudja Brett A. Wagner Justin G. Wilkes Juan Du Joseph J. Cullen Garry R. Buettner Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy Redox Biology |
| title | Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy |
| title_full | Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy |
| title_fullStr | Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy |
| title_full_unstemmed | Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy |
| title_short | Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy |
| title_sort | tumor cells have decreased ability to metabolize h2o2 implications for pharmacological ascorbate in cancer therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2213231716302634 |
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