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PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation

Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Martin Kupiec and Maciej Wnuk
Genes 2021, 12(6), 849;
Received: 11 May 2021 / Revised: 30 May 2021 / Accepted: 31 May 2021 / Published: 31 May 2021
(This article belongs to the Special Issue Mechanisms of DNA Damage, Repair and Mutagenesis)
(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. View Full-Text
Keywords: PARP; kinase inhibitors; ionizing radiation PARP; kinase inhibitors; ionizing radiation
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MDPI and ACS Style

Jonuscheit, S.; Jost, T.; Gajdošová, F.; Wrobel, M.; Hecht, M.; Fietkau, R.; Distel, L. PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation. Genes 2021, 12, 849.

AMA Style

Jonuscheit S, Jost T, Gajdošová F, Wrobel M, Hecht M, Fietkau R, Distel L. PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation. Genes. 2021; 12(6):849.

Chicago/Turabian Style

Jonuscheit, Stephanie; Jost, Tina; Gajdošová, Fritzi; Wrobel, Maximilian; Hecht, Markus; Fietkau, Rainer; Distel, Luitpold. 2021. "PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation" Genes 12, no. 6: 849.

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