{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:43:27Z","timestamp":1783619007591,"version":"3.55.0"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Arginase plays a crucial role in the urea cycle; it also has immunosuppressive and pro\u2010tumor effects. The present study aimed to assess the effects of arginase inhibition by thymoquinone (2\u2010Isopropyl\u20105\u2010methyl\u20101,4\u2010benzoquinone), an active compound of\n                    <jats:italic>Nigella sativa<\/jats:italic>\n                    , on cell death in the MDA\u2010MB\u2010231 triple\u2010negative breast tumor cell line. Cell viability assays, Western blot analysis, and flow cytometry analysis were used to characterize oxidative stress and cell death. Our results showed that inhibition of arginase activity with thymoquinone significantly increased intracellular nitric oxide levels and resulted in overproduction of cellular and mitochondrial reactive oxygen species. Reductions in cell viability, cycle arrest, and increased cell death were also observed. Loss of transmembrane mitochondrial potential, activation of caspase\u20103, \u20107, and \u20109, cleavage of PARP, condensation and\/or fragmentation of the nuclei, suggest that this cell death involved apoptosis. Furthermore, a cytoplasm vacuole formation and an increase in the ratio of [LC3\u2010II\/LC3\u2010I] suggests a concomitant activation of autophagy with apoptosis. Altogether, the present study highlighted that arginase inhibition with thymoquinone induces a hybrid type of cell death defined as oxiapoptophagy. Thus, arginase inhibition with thymoquinone in the MDA\u2010MB\u2010231 cell line could be, in part, involved in the anticancer effect of thymoquinone.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70130","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:45:31Z","timestamp":1737348331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell\u2010Death in MDA\u2010MB\u2010231 Cell Line"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0730-0214","authenticated-orcid":false,"given":"Jaweher","family":"Bday","sequence":"first","affiliation":[{"name":"Molecular Immuno\u2010Oncology Laboratory University of Monastir Monastir Tunisia"},{"name":"Higher Institute of Biotechnology of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4414-1767","authenticated-orcid":false,"given":"Moufida","family":"Souid","sequence":"additional","affiliation":[{"name":"Molecular Immuno\u2010Oncology Laboratory University of Monastir Monastir Tunisia"},{"name":"Higher Institute of Biotechnology of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"Pires","sequence":"additional","affiliation":[{"name":"Bio\u2010PeroxIL \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 Laboratory (EA 7270) Universit\u00e9 de Bourgogne (UB) Dijon France"},{"name":"Centre des Sciences du Go\u00fbt et de l'Alimentation, CNRS, INRAE, Institut Agro Universit\u00e9 de Bourgogne Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sallouha","family":"Gabbouj","sequence":"additional","affiliation":[{"name":"Molecular Immuno\u2010Oncology Laboratory University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-9680","authenticated-orcid":false,"given":"Anne","family":"V\u00e9jux","sequence":"additional","affiliation":[{"name":"Bio\u2010PeroxIL \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 Laboratory (EA 7270) Universit\u00e9 de Bourgogne (UB) Dijon France"},{"name":"Centre des Sciences du Go\u00fbt et de l'Alimentation, CNRS, INRAE, Institut Agro Universit\u00e9 de Bourgogne Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-0172","authenticated-orcid":false,"given":"G\u00e9rard","family":"Lizard","sequence":"additional","affiliation":[{"name":"Bio\u2010PeroxIL \u2018Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism\u2019 Laboratory (EA 7270) Universit\u00e9 de Bourgogne (UB) Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-0091","authenticated-orcid":false,"given":"Elham","family":"Hassen","sequence":"additional","affiliation":[{"name":"Molecular Immuno\u2010Oncology Laboratory University of Monastir Monastir Tunisia"},{"name":"Higher Institute of Biotechnology of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3360001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(97)00099-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0305-0491(95)02138-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00278.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1237"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.03.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112840"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2022.152189"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29814"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.01.046"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40170-022-00301-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100636"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(02)00391-1"},{"key":"e_1_2_10_15_1","unstructured":"R.Singh S.Pervin A.Karimi S.Cederbaum andG.Chaudhuri Arginase Activity in Human Breast Cancer Cell Lines: N(omega)\u2010Hydroxy\u2010L\u2010arginine Selectively Inhibits Cell Proliferation and Induces Apoptosis in MDA\u2010MB\u2010468 Cells. 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