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

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Lacerda, Pammela A. ; Oenning, Luan C. ; Bellato, Guilherme Cuoghi ; Lopes-Santos, Lucilene ; Antunes, Natalicia de Jesus ; Mariz, Bruno Augusto Linhares Almeida ; Teixeira, Gabriela ; Vasconcelos, Rafael ; Simoes, Gustavo Ferreira ; de Souza, Ivani Aparecida ; Pinto, Clovis Antonio Lopes ; Salo, Tuula ; Coletta, Ricardo D. ; Augusto, Taize M. ; de Oliveira, Carine Ervolino ; Cervigne, Nilva K.

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 13, p. 18-pg., 2023-01-05.

Abstract

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.Conclusion: 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 (AU)

• FAPESP's process: 19/09693-5 - "STUDY OF THE ANDROGEN RECEPTOR ACTIVITY ON THE MODULATION OF HEPARANASE IN PROSTATE CANCER"
• Grantee: Taize Machado Augusto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/10029-1 - Use of Institutional Technical Reserve - 2015
• Grantee: Taize Machado Augusto
• Support Opportunities: Research Grants - Technical Reserve for Institutional Research Infrastructure
• FAPESP's process: 18/17495-6 - In vivo study of Polypodium leucotomos phytotherapy effect in oral cancer
• Grantee: Guilherme Cuoghi Bellato
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/21347-7 - Effects of the phytotherapic Polypodium leucotomos on skin cancer: a preliminary investigation on human cell lines
• Grantee: Mariana Ayaka Yamashita
• Support Opportunities: Scholarships in Brazil - Scientific Initiation