Magalie Hervieu, Arnaud J. Legrand, Emilie Floquet, Thierry Idziorek, Corentin Spriet, Didier Monté, Vincent Villeret, Marc Aumercier, Souhaila Choul-li
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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.</p>\n </section>\n \n <section>\n \n <h3> Aims</h3>\n \n <p>The mechanism of the antitumor effect of PARP-1 inhibition was investigated in the Ets-1-expressing MDA-MB-231 breast cancer cells.</p>\n </section>\n \n <section>\n \n <h3> Methods and Results</h3>\n \n <p>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 p47<sup>phox</sup> expression, a subunit of the NAPDH oxidase (NOX).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>These preliminary findings correlate PARPi-induced oxidative DNA damage/oxidative stress to Ets-1 expression in breast cancer cells.</p>\n </section>\n </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 1","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706972/pdf/","citationCount":"0","resultStr":"{\"title\":\"PARP-1 Inhibition Increases Oxidative Stress in Ets-1-Expressing MDA-MB-231 Breast Cancer Cells\",\"authors\":\"Magalie Hervieu, Arnaud J. Legrand, Emilie Floquet, Thierry Idziorek, Corentin Spriet, Didier Monté, Vincent Villeret, Marc Aumercier, Souhaila Choul-li\",\"doi\":\"10.1002/cnr2.70119\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>The mechanism of the antitumor effect of PARP-1 inhibition was investigated in the Ets-1-expressing MDA-MB-231 breast cancer cells.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods and Results</h3>\\n \\n <p>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 p47<sup>phox</sup> expression, a subunit of the NAPDH oxidase (NOX).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>These preliminary findings correlate PARPi-induced oxidative DNA damage/oxidative stress to Ets-1 expression in breast cancer cells.</p>\\n </section>\\n </div>\",\"PeriodicalId\":9440,\"journal\":{\"name\":\"Cancer reports\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-01-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706972/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cnr2.70119\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer reports","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cnr2.70119","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
PARP-1 Inhibition Increases Oxidative Stress in Ets-1-Expressing MDA-MB-231 Breast Cancer Cells
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.
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