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The purpose of this work was to explore graviola extract and its nano-platform\u2019s effects on tongue carcinoma (SCC154 cells) in vitro model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Graviola leaves extract (GLE) was isolated, and its phenolic content was identified. Three nano-formulations (F1-F3) were optimized for GLE delivery, with F1 chosen for its optimal size and stability to synthesize graviola nanoparticles (GNPs). SCC154 cells were split into three groups: group \u0399 (untreated SCC154 cells), group \u0399\u0399: SCC154 cells\u2009+\u2009ethanolic GLE, and group \u0399\u0399\u0399: SCC154 cells\u2009+\u2009GLE encapsulated in a nano-void delivery system (GNPs). In vitro tests assessed cell viability via MTT assay, cell cycle, and apoptosis by flow cytometry, DNA damage using comet assay, and gene expression of the key molecular markers (PI3K, AKT, mTOR, and GSK-3\u03b2) by quantitative real-time polymerase chain reaction. Transmission electron microscopic examination of cells was also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GLE and GNPs reduced SCC154 cells\u2019 proliferation compared to untreated cells, with GNPs showing significantly higher cytotoxicity. Both treatments also induced apoptosis, arrested the cell cycle, and caused DNA damage with a significant pronounced effect in the GNPs-treated group. Gene expression analysis revealed a substantial decline in PI3K, AKT, mTOR, and GSK-3\u03b2 in both treated groups relative to the control group, with a significant downregulation in the GNPs-treated group. Ultrastructural examination revealed severe destruction in tongue carcinoma cells of both treated groups, with substantial damage in the GNPs-treated group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GNPs showed a better impact than GLE in tongue carcinoma therapy, causing cytotoxicity and apoptosis, potentially through the PI3K\/AKT\/mTOR pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12906-025-05113-4","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:42:31Z","timestamp":1759401751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Revealing the anticancer potential of nano-encapsulated graviola extract on tongue carcinoma (SCC154) cell line: targeting the PI3K\/AKT\/mTOR pathway (in vitro study)"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3562-1099","authenticated-orcid":false,"given":"Amany Hany Mohamed","family":"Kamel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-7591","authenticated-orcid":false,"given":"Ahmed A.","family":"Abd-Rabou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-6544","authenticated-orcid":false,"given":"Ahmed","family":"Basuoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-0070","authenticated-orcid":false,"given":"Nermeen","family":"AbuBakr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"issue":"6","key":"5113_CR1","first-page":"394","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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Academic Press. 2015. pp. 655\u201361.","DOI":"10.1016\/B978-0-12-409517-5.00073-5"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-025-05113-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12906-025-05113-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-025-05113-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T12:02:59Z","timestamp":1759406579000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-025-05113-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5113"],"URL":"https:\/\/doi.org\/10.1186\/s12906-025-05113-4","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]},"assertion":[{"value":"13 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was authorized by Cairo University\u2019s Faculty of Dentistry\u2019s Institutional Review Board (approval number: 26\/3\/24) and complies with the institutional policy on experimental research. The study involved only in vitro experiments using a commercially available human tongue carcinoma cell line. No human participants or animals were involved.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"352"}}