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The aim of this study was to evaluate the antitumor and immunomodulatory effects of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Piper nigrum<\/jats:italic>\n                    <\/jats:styled-content>\n                    extract in a murine model of AML, with particular emphasis on its ability to modulate the phosphatidylinositol 3\u2010kinase\/protein kinase B\/mechanistic target of rapamycin (PI3K\/AKT\/mTOR) signaling pathway. The chemical composition of the extract was characterized using advanced analytical techniques. In\u00a0vitro assays were performed to evaluate cytotoxic and cytostatic effects, glucose consumption and ROS production, modulation of Gal\u20109 (galectin 9) and PD\u2010L1 (programmed death\u2010ligand 1), focusing on and relating it to the modulation of the (PI3K\/AKT\/mTOR) pathway. In\u00a0vivo studies were performed using mice inoculated with DA\u20103\/ER\u2010GM cells to evaluate hematological parameters, survival, and immune response after\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. nigrum<\/jats:italic>\n                    <\/jats:styled-content>\n                    treatment.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. nigrum<\/jats:italic>\n                    <\/jats:styled-content>\n                    extract demonstrated cytotoxic and cytostatic activity in\u00a0vitro, characterized by a decrease in cell proliferation and survival possibly associated with modulation of the PI3K\/AKT\/mTOR pathway. In the murine AML model, treatment significantly reduced circulating blasts, improved hematological parameters, and prolonged survival. In addition, an increase in effector memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells was observed, along with a reduction in plasma proinflammatory cytokine levels.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Piper nigrum<\/jats:italic>\n                    <\/jats:styled-content>\n                    may represent a promising complementary therapeutic strategy for AML, acting as an antitumor and immunometabolic modulator. These findings suggest potential clinical applications of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. nigrum<\/jats:italic>\n                    <\/jats:styled-content>\n                    extract as an adjuvant or alternative therapy in the treatment of AML, warranting further preclinical and clinical investigation.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70423","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:45:19Z","timestamp":1787060719000},"page":"5988-6004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>Piper nigrum<\/i>\n                    <\/scp>\n                    Has an Antitumor Effect Through Regulation of the Phosphatidylinositol 3\u2010Kinase Signaling Pathway in a Murine Model of Acute Myeloid Leukemia"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8484-921X","authenticated-orcid":false,"given":"Natalia","family":"Murillo","sequence":"first","affiliation":[{"name":"Grupo de Inmunobiolog\u00eda y Biolog\u00eda Celular, Facultad de Ciencias, Departamento de Microbiolog\u00eda Pontificia Universidad Javeriana  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-3277","authenticated-orcid":false,"given":"Paola","family":"Lasso","sequence":"additional","affiliation":[{"name":"Grupo de Inmunobiolog\u00eda y Biolog\u00eda Celular, Facultad de Ciencias, Departamento de Microbiolog\u00eda Pontificia Universidad Javeriana  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-3181","authenticated-orcid":false,"given":"Claudia","family":"Urue\u00f1a","sequence":"additional","affiliation":[{"name":"Grupo de 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