Journal article
Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma
Antioxidants, Vol.10(12), p.1988
12/14/2021
DOI: 10.3390/antiox10121988
PMCID: PMC8750785
PMID: 34943091
Abstract
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.
Details
- Title: Subtitle
- Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma
- Creators
- Susanne FlorClaudia R OlivaMd Yousuf AliKristen L ColemanJeremy D GreenleeKarra A JonesVarun MongaCorinne E Griguer
- Resource Type
- Journal article
- Publication Details
- Antioxidants, Vol.10(12), p.1988
- DOI
- 10.3390/antiox10121988
- PMID
- 34943091
- PMCID
- PMC8750785
- NLM abbreviation
- Antioxidants (Basel)
- ISSN
- 2076-3921
- eISSN
- 2076-3921
- Grant note
- DOI: 10.13039/100000048, name: American Cancer Society, award: IRG-15-176-41; name: National Institute of Health, award: R01CA160821; DOI: 10.13039/100000002, name: National Institutes of Health, award: R21NS100054
- Language
- English
- Date published
- 12/14/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Neurosurgery; Otolaryngology; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984202160302771
Metrics
18 Record Views