{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:03:06Z","timestamp":1787594586798,"version":"build-2736575974"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Oral cancer refers to malignant tumors, of which 90% are squamous cell carcinomas (OSCCs). These malignancies exhibit rapid progression, poor prognosis, and often mutilating therapeutical approaches. The determination of a prophylactic and\/or therapeutic antitumor role of the polyphenolic extract <jats:italic>Polypodium leucotomos(PL)<\/jats:italic> would be relevant in developing new tools for prevention and treatment.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We aimed to determine the antitumor effect of PL by treating OSCC cell lines with PL metabolites and evaluating its action during OSCC progression <jats:italic>in vivo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> PL treatment successfully impaired cell cycling and proliferation, migration, and invasion, enhanced apoptosis, and modulated macrophage polarization associated with the tumoral immune-inflammatory response of tongue cancer cell lines (TSCC). PL treatment significantly decreased the expression of MMP1 (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) and MMP2 (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), and increased the expression of TIMP1 (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) and TIMP2 (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001) in these cells. The mesenchymal-epithelial transition phenotype was promoted in cells treated with PL, through upregulation of E-CAD (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) and reduction of N-CAD (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). PL restrained OSCC progression <jats:italic>in vivo<\/jats:italic> by inhibiting tumor volume growth and decreasing the number of severe dysplasia lesions and squamous cell carcinomas. Ki-67 was significantly higher expressed in tongue tissues of animals not treated with PL(<jats:italic>p<\/jats:italic> &amp;lt; 0.05), and a notable reduction in Bcl2 (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) and Pcna (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) cell proliferation-associated genes was found in dysplastic lesions and TSCCs of PL-treated mice. Finally, N-cad(Cdh2), Vim, and Twist were significantly reduced in tongue tissues treated with PL.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> PL significantly decreased OSCC carcinogenic processes <jats:italic>in vitro<\/jats:italic> and inhibited tumor progression <jats:italic>in vivo<\/jats:italic>. PL also appears to contribute to the modulation of immune-inflammatory oral tumor-associated responses. Taken together, these results suggest that PL plays an important antitumor role in processes associated with oral carcinogenesis and may be a potential phytotherapeutic target for the prevention and\/or adjuvant treatment of TSCCs<\/jats:p>","DOI":"10.3389\/fphar.2022.1098374","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:26:31Z","timestamp":1672935991000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Polypodium leucotomos targets multiple aspects of oral carcinogenesis and it is a potential antitumor phytotherapy against tongue cancer growth"],"prefix":"10.3389","volume":"13","author":[{"given":"Pammela A.","family":"Lacerda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan C.","family":"Oenning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Cuoghi","family":"Bellato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilene","family":"Lopes-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natal\u00edcia de Jesus","family":"Antunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Augusto Linhares Almeida","family":"Mariz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Vasconcelos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Ferreira","family":"Sim\u00f5es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivani Aparecida","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00f3vis Ant\u00f4nio Lopes","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo D.","family":"Coletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taize M.","family":"Augusto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine Ervolino","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilva K.","family":"Cervigne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"581","DOI":"10.3390\/nu8090581","article-title":"The anti-cancer effect of polyphenols against breast cancer and cancer stem cells: Molecular mechanisms","volume":"8","author":"Abdal Dayem","year":"2016","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1158\/1535-7163.MCT-12-1136","article-title":"The fatty acid synthase inhibitor orlistat reduces the growth and metastasis of orthotopic tongue oral squamous cell carcinomas","volume":"13","author":"Agostini","year":"2014","journal-title":"Mol. 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