PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation
(1) Background: Niraparib and Talazoparib are poly (ADP-ribose) polymerase (PARP) 1/2 inhibitors. It is assumed that combining PARP inhibitors with radiotherapy could be beneficial for cancer treatment. In this study, melanoma cells were treated with Niraparib and Talazoparib in combination with ion...
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doaj-7502151f53e648be98f58cb8b732dcf12021-06-01T01:50:18ZengMDPI AGGenes2073-44252021-05-011284984910.3390/genes12060849PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing RadiationStephanie Jonuscheit0Tina Jost1Fritzi Gajdošová2Maximilian Wrobel3Markus Hecht4Rainer Fietkau5Luitpold Distel6Department of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Radiation Oncology, University Hospital Erlangen, 91054 Erlangen, Germany(1) Background: Niraparib and Talazoparib are poly (ADP-ribose) polymerase (PARP) 1/2 inhibitors. It is assumed that combining PARP inhibitors with radiotherapy could be beneficial for cancer treatment. In this study, melanoma cells were treated with Niraparib and Talazoparib in combination with ionizing radiation (IR). (2) Methods: The effects of Talazoparib and Niraparib in combination with IR on cell death, clonogenicity and cell cycle arrest were studied in healthy primary fibroblasts and primary melanoma cells. (3) Results: The melanoma cells had a higher PARP1 and PARP2 content than the healthy fibroblasts, and further increased their PARP2 content after the combination therapy. PARP inhibitors both sensitized fibroblasts and melanoma cells to IR. A clear supra-additive effect of KI+IR treatment was detected in two melanoma cell lines analyzing the surviving fraction. The cell death rate increased in the healthy fibroblasts, but to a larger extent in melanoma cells after combined treatment. Finally, a lower percentage of cells in the radiosensitive G2/M phase is present in the healthy fibroblasts compared to the melanoma cells. (4) Conclusions: Both PARP inhibitors sensitize melanoma cells to IR. Healthy tissue seems to be less affected than melanoma cells. However, the great heterogeneity of the results suggests prior testing of the tumor cells in order to personalize the treatment.https://www.mdpi.com/2073-4425/12/6/849PARPkinase inhibitorsionizing radiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stephanie Jonuscheit Tina Jost Fritzi Gajdošová Maximilian Wrobel Markus Hecht Rainer Fietkau Luitpold Distel |
spellingShingle |
Stephanie Jonuscheit Tina Jost Fritzi Gajdošová Maximilian Wrobel Markus Hecht Rainer Fietkau Luitpold Distel PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation Genes PARP kinase inhibitors ionizing radiation |
author_facet |
Stephanie Jonuscheit Tina Jost Fritzi Gajdošová Maximilian Wrobel Markus Hecht Rainer Fietkau Luitpold Distel |
author_sort |
Stephanie Jonuscheit |
title |
PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation |
title_short |
PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation |
title_full |
PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation |
title_fullStr |
PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation |
title_full_unstemmed |
PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation |
title_sort |
parp inhibitors talazoparib and niraparib sensitize melanoma cells to ionizing radiation |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-05-01 |
description |
(1) Background: Niraparib and Talazoparib are poly (ADP-ribose) polymerase (PARP) 1/2 inhibitors. It is assumed that combining PARP inhibitors with radiotherapy could be beneficial for cancer treatment. In this study, melanoma cells were treated with Niraparib and Talazoparib in combination with ionizing radiation (IR). (2) Methods: The effects of Talazoparib and Niraparib in combination with IR on cell death, clonogenicity and cell cycle arrest were studied in healthy primary fibroblasts and primary melanoma cells. (3) Results: The melanoma cells had a higher PARP1 and PARP2 content than the healthy fibroblasts, and further increased their PARP2 content after the combination therapy. PARP inhibitors both sensitized fibroblasts and melanoma cells to IR. A clear supra-additive effect of KI+IR treatment was detected in two melanoma cell lines analyzing the surviving fraction. The cell death rate increased in the healthy fibroblasts, but to a larger extent in melanoma cells after combined treatment. Finally, a lower percentage of cells in the radiosensitive G2/M phase is present in the healthy fibroblasts compared to the melanoma cells. (4) Conclusions: Both PARP inhibitors sensitize melanoma cells to IR. Healthy tissue seems to be less affected than melanoma cells. However, the great heterogeneity of the results suggests prior testing of the tumor cells in order to personalize the treatment. |
topic |
PARP kinase inhibitors ionizing radiation |
url |
https://www.mdpi.com/2073-4425/12/6/849 |
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