{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T22:54:54Z","timestamp":1783810494142,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T00:00:00Z","timestamp":1677974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation (SNSF)","doi-asserted-by":"publisher","award":["SNF IZSTZ0_198887"],"award-info":[{"award-number":["SNF IZSTZ0_198887"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation (SNSF)","doi-asserted-by":"publisher","award":["BEPE2020\/01381-1"],"award-info":[{"award-number":["BEPE2020\/01381-1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The S\u00e3o Paulo Research Foundation (FAPESP)","award":["SNF IZSTZ0_198887"],"award-info":[{"award-number":["SNF IZSTZ0_198887"]}]},{"name":"The S\u00e3o Paulo Research Foundation (FAPESP)","award":["BEPE2020\/01381-1"],"award-info":[{"award-number":["BEPE2020\/01381-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cystathionine \u03b2-synthase (CBS), CSE (cystathionine \u03b3-lyase) and 3-mercaptopyruvate sulfurtransferase (3-MST) have emerged as three significant sources of hydrogen sulfide (H2S) in various forms of mammalian cancer. Here, we investigated the functional role of CBS\u2019 and 3-MST\u2019s catalytic activity in the murine breast cancer cell line EO771. The CBS\/CSE inhibitor aminooxyacetic acid (AOAA) and the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) were used to assess the role of endogenous H2S in the modulation of breast cancer cell proliferation, migration, bioenergetics and viability in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux analysis). CBS and 3-MST, as well as expression were detected by Western blotting; H2S production was measured by the fluorescent dye AzMC. The results show that EO771 cells express CBS, CSE and 3-MST protein, as well as several enzymes involved in H2S degradation (SQR, TST, and ETHE1). Pharmacological inhibition of CBS or 3-MST inhibited H2S production, suppressed cellular bioenergetics and attenuated cell proliferation. Cell migration was only inhibited by the 3-MST inhibitor, but not the CBS\/CSE inhibitor. Inhibition of CBS\/CSE of 3-MST did not significantly affect basal cell viability; inhibition of 3-MST (but not of CBS\/CSE) slightly enhanced the cytotoxic effects of oxidative stress (hydrogen peroxide challenge). From these findings, we conclude that endogenous H2S, generated by 3-MST and to a lower degree by CBS\/CSE, significantly contributes to the maintenance of bioenergetics, proliferation and migration in murine breast cancer cells and may also exert a minor role as a cytoprotectant.<\/jats:p>","DOI":"10.3390\/antiox12030647","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T05:18:43Z","timestamp":1678079923000},"page":"647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Role of Cystathionine \u03b2-Synthase and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics of Murine Breast Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-9881","authenticated-orcid":false,"given":"Sidneia Sousa","family":"Santos","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023, Brazil"},{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-290X","authenticated-orcid":false,"given":"Larissa de Oliveira Cavalcanti Peres","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Federal University of S\u00e3o Paulo (EPM\/UNIFESP), S\u00e3o Paulo 04023, Brazil"},{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Martins","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7875-5954","authenticated-orcid":false,"given":"Maria","family":"Petrosino","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-1817","authenticated-orcid":false,"given":"Karim","family":"Zuhra","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6693-6897","authenticated-orcid":false,"given":"Kelly","family":"Ascen\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8055-6970","authenticated-orcid":false,"given":"Abhishek","family":"Anand","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3584-0045","authenticated-orcid":false,"given":"Reham Mahmoud","family":"Abdel-Kader","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-8628","authenticated-orcid":false,"given":"Mohamed Z.","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-4583","authenticated-orcid":false,"given":"Carole","family":"Bourquin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-4235","authenticated-orcid":false,"given":"Csaba","family":"Szabo","sequence":"additional","affiliation":[{"name":"Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1124\/pr.117.014050","article-title":"International union of basic and clinical pharmacology. 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