Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells
Fusion-positive rhabdomyosarcoma (FP-RMS) is a highly aggressive childhood malignancy which is mainly treated by conventional chemotherapy, surgery and radiation therapy. Since radiotherapy is associated with a high burden of late side effects in pediatric patients, addition of radiosensitizers woul...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.664462/full |
| _version_ | 1818407078749798400 |
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| author | Eva Brack Eva Brack Eva Brack Sabine Bender Marco Wachtel Marco Wachtel Martin Pruschy Beat W. Schäfer Beat W. Schäfer |
| author_facet | Eva Brack Eva Brack Eva Brack Sabine Bender Marco Wachtel Marco Wachtel Martin Pruschy Beat W. Schäfer Beat W. Schäfer |
| author_sort | Eva Brack |
| collection | DOAJ |
| description | Fusion-positive rhabdomyosarcoma (FP-RMS) is a highly aggressive childhood malignancy which is mainly treated by conventional chemotherapy, surgery and radiation therapy. Since radiotherapy is associated with a high burden of late side effects in pediatric patients, addition of radiosensitizers would be beneficial. Here, we thought to assess the role of fenretinide, a potential agent for FP-RMS treatment, as radiosensitizer. Survival of human FP-RMS cells was assessed after combination therapy with fenretinide and ionizing radiation (IR) by cell viability and clonogenicity assays. Indeed, this was found to significantly reduce cell viability compared to single treatments. Mechanistically, this was accompanied by enhanced production of reactive oxygen species, initiation of cell cycle arrest and induction of apoptosis. Interestingly, the combination treatment also triggered a new form of dynamin-dependent macropinocytosis, which was previously described in fenretinide-only treated cells. Our data suggest that fenretinide acts in combination with IR to induce cell death in FP-RMS cells and therefore might represent a novel radiosensitizer for the treatment of this disease. |
| first_indexed | 2024-12-14T09:22:07Z |
| format | Article |
| id | doaj.art-55c2d2e34cfa4e51b78478eba3aba030 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T09:22:07Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-55c2d2e34cfa4e51b78478eba3aba0302022-12-21T23:08:17ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.664462664462Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma CellsEva Brack0Eva Brack1Eva Brack2Sabine Bender3Marco Wachtel4Marco Wachtel5Martin Pruschy6Beat W. Schäfer7Beat W. Schäfer8Department of Oncology, Children’s Research Center, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center, University Children’s Hospital Zurich, Zurich, SwitzerlandPediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Radiology Biology, University Hospital Zurich, Radio-Oncology, Zurich, SwitzerlandDepartment of Oncology, Children’s Research Center, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center, University Children’s Hospital Zurich, Zurich, SwitzerlandDepartment of Radiology Biology, University Hospital Zurich, Radio-Oncology, Zurich, SwitzerlandDepartment of Oncology, Children’s Research Center, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center, University Children’s Hospital Zurich, Zurich, SwitzerlandFusion-positive rhabdomyosarcoma (FP-RMS) is a highly aggressive childhood malignancy which is mainly treated by conventional chemotherapy, surgery and radiation therapy. Since radiotherapy is associated with a high burden of late side effects in pediatric patients, addition of radiosensitizers would be beneficial. Here, we thought to assess the role of fenretinide, a potential agent for FP-RMS treatment, as radiosensitizer. Survival of human FP-RMS cells was assessed after combination therapy with fenretinide and ionizing radiation (IR) by cell viability and clonogenicity assays. Indeed, this was found to significantly reduce cell viability compared to single treatments. Mechanistically, this was accompanied by enhanced production of reactive oxygen species, initiation of cell cycle arrest and induction of apoptosis. Interestingly, the combination treatment also triggered a new form of dynamin-dependent macropinocytosis, which was previously described in fenretinide-only treated cells. Our data suggest that fenretinide acts in combination with IR to induce cell death in FP-RMS cells and therefore might represent a novel radiosensitizer for the treatment of this disease.https://www.frontiersin.org/articles/10.3389/fonc.2021.664462/fullrhabdomyosarcomachildhood cancerfenretinideradiation therapyradiosensitizerreactive oxygen species |
| spellingShingle | Eva Brack Eva Brack Eva Brack Sabine Bender Marco Wachtel Marco Wachtel Martin Pruschy Beat W. Schäfer Beat W. Schäfer Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells Frontiers in Oncology rhabdomyosarcoma childhood cancer fenretinide radiation therapy radiosensitizer reactive oxygen species |
| title | Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells |
| title_full | Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells |
| title_fullStr | Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells |
| title_full_unstemmed | Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells |
| title_short | Fenretinide Acts as Potent Radiosensitizer for Treatment of Rhabdomyosarcoma Cells |
| title_sort | fenretinide acts as potent radiosensitizer for treatment of rhabdomyosarcoma cells |
| topic | rhabdomyosarcoma childhood cancer fenretinide radiation therapy radiosensitizer reactive oxygen species |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.664462/full |
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