PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells
ABSTRACT Background The Ets‐1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated in cancer progression. In a previous study, we revealed that poly(ADP‐ribose) polymerase‐1 (PARP‐1) inhibition by PJ‐34 results in Ets‐1 level increase in cells, which...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.70119 |
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| author | Magalie Hervieu Arnaud J. Legrand Emilie Floquet Thierry Idziorek Corentin Spriet Didier Monté Vincent Villeret Marc Aumercier Souhaila Choul‐li |
| author_facet | Magalie Hervieu Arnaud J. Legrand Emilie Floquet Thierry Idziorek Corentin Spriet Didier Monté Vincent Villeret Marc Aumercier Souhaila Choul‐li |
| author_sort | Magalie Hervieu |
| collection | DOAJ |
| description | ABSTRACT Background The Ets‐1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated in cancer progression. In a previous study, we revealed that poly(ADP‐ribose) polymerase‐1 (PARP‐1) inhibition by PJ‐34 results in Ets‐1 level increase in cells, which is related with cell death of Ets‐1‐expressing cancer cells. Aims The mechanism of the antitumor effect of PARP‐1 inhibition was investigated in the Ets‐1‐expressing MDA‐MB‐231 breast cancer cells. Methods and Results We tested the effects of four PARP inhibitors (PARPi) (PJ‐34, Veliparib, Olaparib, and Rucaparib). We first demonstrated that PARPi reduced cells growth through G2/M cell cycle arrest. Next, we evaluated PARP‐1 inhibition effect on oxidative DNA damage in Ets‐1‐overexpressing and Ets‐1‐non‐expressing breast cancer cells and we showed that PARPi led only Ets‐1‐overexpressing cells to accumulate it, which triggers the DNA damage response as revealed by the increase in the level of a panel of DNA damage‐related proteins. Importantly, we demonstrated that PARPi increased reactive oxygen species (ROS), only in Ets‐1‐overexpressing cells and this is accompanied by upregulation of p47phox expression, a subunit of the NAPDH oxidase (NOX). Conclusion These preliminary findings correlate PARPi‐induced oxidative DNA damage/oxidative stress to Ets‐1 expression in breast cancer cells. |
| format | Article |
| id | doaj-art-1671f438c8eb49a98997ce314fa7d402 |
| institution | Kabale University |
| issn | 2573-8348 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj-art-1671f438c8eb49a98997ce314fa7d4022025-01-30T15:46:35ZengWileyCancer Reports2573-83482025-01-0181n/an/a10.1002/cnr2.70119PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer CellsMagalie Hervieu0Arnaud J. Legrand1Emilie Floquet2Thierry Idziorek3Corentin Spriet4Didier Monté5Vincent Villeret6Marc Aumercier7Souhaila Choul‐li8CNRS EMR9002 Integrative Structural Biology Lille FranceCNRS EMR9002 Integrative Structural Biology Lille FranceCNRS EMR9002 Integrative Structural Biology Lille FranceUniv. Lille, CNRS, Inserm, CHU Lille UMR9020‐U1277‐CANTHER‐Cancer Heterogeneity Plasticity and Resistance to Therapies Lille FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US41‐UMS2014‐PLBS, F‐59000, Lille, France; Univ. Lille, CNRS UMR8576‐UGSF‐Structural and Functional Glycobiology Unit Lille FranceCNRS EMR9002 Integrative Structural Biology Lille FranceCNRS EMR9002 Integrative Structural Biology Lille FranceCNRS EMR9002 Integrative Structural Biology Lille FranceDépartement de Biologie, Faculté des Sciences Université Chouaïb Doukkali El Jadida MoroccoABSTRACT Background The Ets‐1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated in cancer progression. In a previous study, we revealed that poly(ADP‐ribose) polymerase‐1 (PARP‐1) inhibition by PJ‐34 results in Ets‐1 level increase in cells, which is related with cell death of Ets‐1‐expressing cancer cells. Aims The mechanism of the antitumor effect of PARP‐1 inhibition was investigated in the Ets‐1‐expressing MDA‐MB‐231 breast cancer cells. Methods and Results We tested the effects of four PARP inhibitors (PARPi) (PJ‐34, Veliparib, Olaparib, and Rucaparib). We first demonstrated that PARPi reduced cells growth through G2/M cell cycle arrest. Next, we evaluated PARP‐1 inhibition effect on oxidative DNA damage in Ets‐1‐overexpressing and Ets‐1‐non‐expressing breast cancer cells and we showed that PARPi led only Ets‐1‐overexpressing cells to accumulate it, which triggers the DNA damage response as revealed by the increase in the level of a panel of DNA damage‐related proteins. Importantly, we demonstrated that PARPi increased reactive oxygen species (ROS), only in Ets‐1‐overexpressing cells and this is accompanied by upregulation of p47phox expression, a subunit of the NAPDH oxidase (NOX). Conclusion These preliminary findings correlate PARPi‐induced oxidative DNA damage/oxidative stress to Ets‐1 expression in breast cancer cells.https://doi.org/10.1002/cnr2.70119breast cancer cellsDNA damageEts‐1 transcription factoroxidative stressPARP‐1 inhibitors |
| spellingShingle | Magalie Hervieu Arnaud J. Legrand Emilie Floquet Thierry Idziorek Corentin Spriet Didier Monté Vincent Villeret Marc Aumercier Souhaila Choul‐li PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells Cancer Reports breast cancer cells DNA damage Ets‐1 transcription factor oxidative stress PARP‐1 inhibitors |
| title | PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells |
| title_full | PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells |
| title_fullStr | PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells |
| title_full_unstemmed | PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells |
| title_short | PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells |
| title_sort | parp 1 inhibition increases oxidative stress in ets 1 expressing mda mb 231 breast cancer cells |
| topic | breast cancer cells DNA damage Ets‐1 transcription factor oxidative stress PARP‐1 inhibitors |
| url | https://doi.org/10.1002/cnr2.70119 |
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