{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:36:17Z","timestamp":1790876177981,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bios-Therapy: Physiological Systems for Health S.P.A.","award":["D\u2019ATENEO PER LA RICERCA DI BASE 2019"],"award-info":[{"award-number":["D\u2019ATENEO PER LA RICERCA DI BASE 2019"]}]},{"name":"Bios-Therapy: Physiological Systems for Health S.P.A.","award":["ECS00000041\u2014VITALITY"],"award-info":[{"award-number":["ECS00000041\u2014VITALITY"]}]},{"name":"University of Perugia","award":["D\u2019ATENEO PER LA RICERCA DI BASE 2019"],"award-info":[{"award-number":["D\u2019ATENEO PER LA RICERCA DI BASE 2019"]}]},{"name":"University of Perugia","award":["ECS00000041\u2014VITALITY"],"award-info":[{"award-number":["ECS00000041\u2014VITALITY"]}]},{"name":"European Union-NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem","award":["D\u2019ATENEO PER LA RICERCA DI BASE 2019"],"award-info":[{"award-number":["D\u2019ATENEO PER LA RICERCA DI BASE 2019"]}]},{"name":"European Union-NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem","award":["ECS00000041\u2014VITALITY"],"award-info":[{"award-number":["ECS00000041\u2014VITALITY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intracellular alkalosis and extracellular acidosis are two pathological features associated with malignant cells. They offer advantages in terms of invasiveness and proliferation. Extracellular acidification is the consequence of intracellular metabolic changes associated with a higher metabolic rate of cancer cells, potentially inducing dangerous intracellular acidification. To overcome this menace, malignant cells adapt themselves to export hydrogen ions. Therefore, it is reasonable that targeting intracellular alkalinization and extracellular acidification to prompt the reversal of such a pH gradient towards a condition comparable to normal, untransformed cells may represent a strategy helping to contrast malignant behavior. In the present study, we investigated in vitro, in prostate cancer cell models, the biological activity towards intracellular, extracellular and organelle pH of systems of molecules of vegetal origin. A few of these systems were shown to promote intracellular acidification in vitro, whereas others were shown to prevent extracellular acidification and promote lysosomal alkalinization in a cell type-dependent manner. This result clearly indicates that these systems may function as agents interfering with malignant cells inverted pH gradient. Further analysis would be necessary to unravel the cell type specificity of their effects, as well as their mechanism of action. Nevertheless, our proof-of-principle study provides evidence that such systems of molecules can be considered interesting agents in co-adjuvating anti-cancer therapies.<\/jats:p>","DOI":"10.3390\/ijms26167700","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T15:30:52Z","timestamp":1754667052000},"page":"7700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting pH Inversion in Prostate Cancer Cells: A Role for Systems of Molecules of Vegetal Origin"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-8476","authenticated-orcid":false,"given":"Lorena","family":"Urbanelli","sequence":"first","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Perugia, Italy"},{"name":"Centro di Eccellenza sui Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, 06123 Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3357-2171","authenticated-orcid":false,"given":"Krizia","family":"Sagini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Perugia, Italy"},{"name":"Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0899-2975","authenticated-orcid":false,"given":"Federica","family":"Delo","sequence":"additional","affiliation":[{"name":"Bios-Therapy, Physiological Systems for Health S.P.A., Loc. 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