TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma
Glioblastoma (GBM) is a brain tumor characterized by poor therapeutic response and overall survival. Despite relevant progress in conventional treatments represented by the clinical use of temozolomide (TMZ), a combination of approaches might be a possible future direction for treating GBM. Transfor...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/1/41 |
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| author | Michela Campolo Marika Lanza Giovanna Casili Irene Paterniti Alessia Filippone Maria Caffo Salvatore M. Cardali Ivana Puliafito Cristina Colarossi Gabriele Raciti Salvatore Cuzzocrea Emanuela Esposito |
| author_facet | Michela Campolo Marika Lanza Giovanna Casili Irene Paterniti Alessia Filippone Maria Caffo Salvatore M. Cardali Ivana Puliafito Cristina Colarossi Gabriele Raciti Salvatore Cuzzocrea Emanuela Esposito |
| author_sort | Michela Campolo |
| collection | DOAJ |
| description | Glioblastoma (GBM) is a brain tumor characterized by poor therapeutic response and overall survival. Despite relevant progress in conventional treatments represented by the clinical use of temozolomide (TMZ), a combination of approaches might be a possible future direction for treating GBM. Transforming growth factor-beta-activated kinase-1 (TAK1) is an essential component in genotoxic stresses-induced NF-κB-activation and mitogen-activated protein kinase (MAPK)-pathways; however, the role of TAK1 in GBM-chemoresistance remains unknown. This study aimed to verify, in GBM human cell lines, in an in vivo U87-xenograft model and in TMZ-treated-patients, the effect of TAK1 inhibition on the sensitivity of GBM cells to chemotherapy. In vitro model, using GBM cell lines, showed that 5Z-7-oxozeaenol augmented the cytotoxic effects of TMZ, blocking TMZ-induced NF-κB-activation, reducing DNA-damage and enhancing TMZ-induced apoptosis in GMB cell lines. We showed a reduction in tumor burden as well as tumor volume in the xenograft model following the treatment with 5Z-7-oxozaenol associated with TMZ. Our results showed a significant up-regulation in TAK1, p-p38, p-JNK and NF-κB in glioblastoma TMZ-treated-patients and denoted the role of 5Z-7-oxozeaenol in increasing the sensitivity of GBM cells to chemotherapy, proving to be an effective coadjuvant to current GBM chemotherapeutic regimens, suggesting a new option for therapeutic treatment of GBM. |
| first_indexed | 2024-03-10T13:46:06Z |
| format | Article |
| id | doaj.art-09fb468706744c1f8793938362198c15 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:46:06Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-09fb468706744c1f8793938362198c152023-11-21T02:33:38ZengMDPI AGCancers2072-66942020-12-011314110.3390/cancers13010041TAK1 Inhibitor Enhances the Therapeutic Treatment for GlioblastomaMichela Campolo0Marika Lanza1Giovanna Casili2Irene Paterniti3Alessia Filippone4Maria Caffo5Salvatore M. Cardali6Ivana Puliafito7Cristina Colarossi8Gabriele Raciti9Salvatore Cuzzocrea10Emanuela Esposito11Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morpho-Functional Imaging, Unit of Neurosurgery, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morpho-Functional Imaging, Unit of Neurosurgery, University of Messina, 98122 Messina, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Viagrande, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Viagrande, ItalyIOM Ricerca S.r.l., Via Penninazzo 11, 95029 Viagrande, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyGlioblastoma (GBM) is a brain tumor characterized by poor therapeutic response and overall survival. Despite relevant progress in conventional treatments represented by the clinical use of temozolomide (TMZ), a combination of approaches might be a possible future direction for treating GBM. Transforming growth factor-beta-activated kinase-1 (TAK1) is an essential component in genotoxic stresses-induced NF-κB-activation and mitogen-activated protein kinase (MAPK)-pathways; however, the role of TAK1 in GBM-chemoresistance remains unknown. This study aimed to verify, in GBM human cell lines, in an in vivo U87-xenograft model and in TMZ-treated-patients, the effect of TAK1 inhibition on the sensitivity of GBM cells to chemotherapy. In vitro model, using GBM cell lines, showed that 5Z-7-oxozeaenol augmented the cytotoxic effects of TMZ, blocking TMZ-induced NF-κB-activation, reducing DNA-damage and enhancing TMZ-induced apoptosis in GMB cell lines. We showed a reduction in tumor burden as well as tumor volume in the xenograft model following the treatment with 5Z-7-oxozaenol associated with TMZ. Our results showed a significant up-regulation in TAK1, p-p38, p-JNK and NF-κB in glioblastoma TMZ-treated-patients and denoted the role of 5Z-7-oxozeaenol in increasing the sensitivity of GBM cells to chemotherapy, proving to be an effective coadjuvant to current GBM chemotherapeutic regimens, suggesting a new option for therapeutic treatment of GBM.https://www.mdpi.com/2072-6694/13/1/41TAK1temozolomideglioblastomacell linespatients |
| spellingShingle | Michela Campolo Marika Lanza Giovanna Casili Irene Paterniti Alessia Filippone Maria Caffo Salvatore M. Cardali Ivana Puliafito Cristina Colarossi Gabriele Raciti Salvatore Cuzzocrea Emanuela Esposito TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma Cancers TAK1 temozolomide glioblastoma cell lines patients |
| title | TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma |
| title_full | TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma |
| title_fullStr | TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma |
| title_full_unstemmed | TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma |
| title_short | TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma |
| title_sort | tak1 inhibitor enhances the therapeutic treatment for glioblastoma |
| topic | TAK1 temozolomide glioblastoma cell lines patients |
| url | https://www.mdpi.com/2072-6694/13/1/41 |
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