University of Oulu

Lacerda PA, Oenning LC, Bellato GC, Lopes-Santos L, Antunes NdJ, Mariz BALA, Teixeira G, Vasconcelos R, Simões GF, de Souza IA, Pinto CAL, Salo T, Coletta RD, Augusto TM, de Oliveira CE and Cervigne NK (2023) Polypodium leucotomos targets multiple aspects of oral carcinogenesis and it is a potential antitumor phytotherapy against tongue cancer growth. Front. Pharmacol. 13:1098374. doi: 10.3389/fphar.2022.1098374

Polypodium leucotomos targets multiple aspects of oral carcinogenesis and it is a potential antitumor phytotherapy against tongue cancer growth

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Author: Lacerda, Pammela A.1; Oenning, Luan C.1; Bellato, Guilherme Cuoghi1;
Organizations: 1Laboratory of Molecular Biology and Cell Culture (LBMCC), Faculty of Medicine of Jundiaí (FMJ), Jundiaí, Brazil
2Laboratory of Pharmacology, University of Campinas, Campinas, Brazil
3Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil
4Department of Morphology, Faculty of Medicine of São Paulo Santa Casa, São Paulo, Brazil
5Department of Physiology, Faculty of Medicine of Jundiaí (FMJ), São Paulo, Brazil
6Graduate Program in Health Sciences, Faculty of Medicine of Jundiaí (FMJ), São Paulo, Brazil
7Department of Morphology and Basic Pathology, Faculty of Medicine of Jundiaí (FMJ), São Paulo, Brazil
8Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
9Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, Brazil
10Department of Internal Medicine, Faculty of Medicine of Jundiaí (FMJ), São Paulo, Brazil
11Department of Pathology and Parasitology, Universidade Federal de Alfenas (UNIFAL), Alfenas, Brazil
12Graduate Program in Biological Science, Universidade Federal de Alfenas (UNIFAL), Alfenas, Brazil
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.2 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-07-05


Introduction: 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 Polypodium leucotomos(PL) would be relevant in developing new tools for prevention and treatment.

Methods: We aimed to determine the antitumor effect of PL by treating OSCC cell lines with PL metabolites and evaluating its action during OSCC progression in vivo.

Results: 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 (p < 0.01) and MMP2 (p < 0.001), and increased the expression of TIMP1 (p < 0.001) and TIMP2 (p < 0.0001) in these cells. The mesenchymal-epithelial transition phenotype was promoted in cells treated with PL, through upregulation of E-CAD (p < 0.001) and reduction of N-CAD (p < 0.05). PL restrained OSCC progression in vivo 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(p < 0.05), and a notable reduction in Bcl2 (p < 0.05) and Pcna (p < 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.

Conclusions: PL significantly decreased OSCC carcinogenic processes in vitro and inhibited tumor progression in vivo. 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.

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Series: Frontiers in pharmacology
ISSN: 1663-9812
ISSN-E: 1663-9812
ISSN-L: 1663-9812
Volume: 13
Article number: 1098374
DOI: 10.3389/fphar.2022.1098374
Type of Publication: A1 Journal article – refereed
Field of Science: 313 Dentistry
Funding: This work was supported by grants from the São Paulo Research Foundation–FAPESP, São Paulo, Brazil (2018/17495-6 for GC and 2019/09693-5 for TMA, 2015/10029-1 and 2016/21347-7 for NKC), and from the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil (88882.457210/2019-01 for PL and 88882.317191/2019-01 for LS).
Copyright information: © 2023 Lacerda, Oenning, Bellato, Lopes-Santos, Antunes, Mariz, Teixeira, Vasconcelos, Simões, de Souza, Pinto, Salo, Coletta, Augusto, de Oliveira and Cervigne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.