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In the present study, the aim was to investigate the potential role of sanguinarine as a specific inhibitor of <jats:italic>Leishmania<\/jats:italic> PP2C that can induce apoptosis in the parasite. The results demonstrated that sanguinarine inhibits, in a dose-dependent mode at 72\u00a0h, the growth and phosphatase activity of both <jats:italic>Leishmania major<\/jats:italic> and <jats:italic>Leishmania mexicana<\/jats:italic> promastigotes. Therefore, all assays were performed from this time period onwards. TUNEL assay was used to identify apoptosis and indicated apoptosis in <jats:italic>L. major<\/jats:italic> and <jats:italic>L. mexicana<\/jats:italic> promastigotes. Similarly, Western blot assay showed that PARP, a DNA damage indicator molecule, was present in <jats:italic>L. major<\/jats:italic> and <jats:italic>L. mexicana<\/jats:italic> promastigotes incubated with the inhibitor. In addition, differential expression of the proapoptotic protein Bax and the antiapoptotic protein Bcl-2 was observed in both <jats:italic>Leishmania<\/jats:italic> species. Finally, the protein phosphatase PP2C expression was not affected, whereas p38 MAPK phosphorylation was increased in <jats:italic>L. major<\/jats:italic> promastigotes than in <jats:italic>L. mexicana<\/jats:italic> promastigotes. Therefore, sanguinarine proved to be an inhibitor of the growth and PP2C enzymatic activity of <jats:italic>L. major<\/jats:italic> and <jats:italic>L. mexicana<\/jats:italic> promastigotes, and with it, this inhibition induced apoptosis.<\/jats:p>","DOI":"10.1007\/s11686-024-00977-x","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T13:55:49Z","timestamp":1737726949000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Potential Role of Sanguinarine as an Inhibitor of Leishmania PP2C in the Induction of Apoptosis"],"prefix":"10.1007","volume":"70","author":[{"given":"M.","family":"Ornelas-Cruces","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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