Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma
Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we asse...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/12/1988 |
| _version_ | 1797506902531244032 |
|---|---|
| author | Susanne Flor Claudia R. Oliva Md Yousuf Ali Kristen L. Coleman Jeremy D. Greenlee Karra A. Jones Varun Monga Corinne E. Griguer |
| author_facet | Susanne Flor Claudia R. Oliva Md Yousuf Ali Kristen L. Coleman Jeremy D. Greenlee Karra A. Jones Varun Monga Corinne E. Griguer |
| author_sort | Susanne Flor |
| collection | DOAJ |
| description | Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma. |
| first_indexed | 2024-03-10T04:39:03Z |
| format | Article |
| id | doaj.art-e470bfc0424d4aeaa02e4939e1e2ef87 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:39:03Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e470bfc0424d4aeaa02e4939e1e2ef872023-11-23T03:33:58ZengMDPI AGAntioxidants2076-39212021-12-011012198810.3390/antiox10121988Catalase Overexpression Drives an Aggressive Phenotype in GlioblastomaSusanne Flor0Claudia R. Oliva1Md Yousuf Ali2Kristen L. Coleman3Jeremy D. Greenlee4Karra A. Jones5Varun Monga6Corinne E. Griguer7Free Radical & Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa, IA 52242, USAFree Radical & Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa, IA 52242, USAInterdisciplinary Graduate Program in Human Toxicology, Department of Radiation Oncology, University of Iowa, Iowa, IA 52242, USAHolden Comprehensive Cancer Center, University of Iowa, Iowa, IA 52242, USADepartment of Neurosurgery, University of Iowa, Iowa, IA 52242, USADepartment of Pathology, University of Iowa, Iowa, IA 52242, USADepartment of Internal Medicine, University of Iowa, Iowa, IA 52242, USAFree Radical & Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa, IA 52242, USAGlioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma.https://www.mdpi.com/2076-3921/10/12/1988catalaseglioblastoma multiformereactive oxygen species (ROS)hydrogen peroxideradiationtemozolomide |
| spellingShingle | Susanne Flor Claudia R. Oliva Md Yousuf Ali Kristen L. Coleman Jeremy D. Greenlee Karra A. Jones Varun Monga Corinne E. Griguer Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma Antioxidants catalase glioblastoma multiforme reactive oxygen species (ROS) hydrogen peroxide radiation temozolomide |
| title | Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma |
| title_full | Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma |
| title_fullStr | Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma |
| title_full_unstemmed | Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma |
| title_short | Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma |
| title_sort | catalase overexpression drives an aggressive phenotype in glioblastoma |
| topic | catalase glioblastoma multiforme reactive oxygen species (ROS) hydrogen peroxide radiation temozolomide |
| url | https://www.mdpi.com/2076-3921/10/12/1988 |
| work_keys_str_mv | AT susanneflor catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT claudiaroliva catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT mdyousufali catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT kristenlcoleman catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT jeremydgreenlee catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT karraajones catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT varunmonga catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma AT corinneegriguer catalaseoverexpressiondrivesanaggressivephenotypeinglioblastoma |