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

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

Emerging Drug Combinations for Targeting Tongue Neoplasms Associated Proteins/Genes: Employing Graph Neural Networks within the RAIN Protocol

“…The research revealed that within tongue cancer cells, FAM168A, also recognized as tongue cancer resistance-associated protein (TCRP1), has the ability to directly associate with AKT1, influencing the regulation of AKT1/NFκB signaling pathways. Furthermore, the study demonstrated FAM168A’s potential function as a connecting protein, binding both to BCR-ABL1 and AKT1, thereby facilitating downstream signaling pathways in CML 1,8,9…”

“…The research revealed that within tongue cancer cells, FAM168A, also recognized as tongue cancer resistance-associated protein (TCRP1), has the ability to directly associate with AKT1, influencing the regulation of AKT1/NFκB signaling pathways. Furthermore, the study demonstrated FAM168A's potential function as a connecting protein, binding both to BCR-ABL1 and AKT1, thereby facilitating downstream signaling pathways in CML 1 , 8 , 9 The genes LncKRT16P6 function as promoters in the advancement of tongue squamous cell carcinoma by acting as sponges for miR-3180 and modulating GATAD2A expression. The study findings demonstrate that LncKRT16P6 boosts the growth, movement, and infiltration of tongue squamous cell carcinoma cells through its interaction with miR-3180, thereby regulating the expression of GATAD2A.…”

Clinical Applications of Polypodium leucotomos (Fernblock®): An Update

“…Finally, it is worth highlighting the recent findings of Lacerda et al (2023) in the field of oral cancer prevention. Their study demosntrated that PLE has the ability to suppress oral cancer cell growth in vitro in SCC-9, SCC-15, and SCC-25 cell lines, and prevent tumor development in vivo in mice with induced oral carcinogenesis.…”

Clinical Applications of Polypodium leucotomos (Fernblock®): An Update

“…A decrease in the expression of Ki67 and PCNA proliferating markers as well as in N-cad (Cdh2), Vim and Twist markers related to migration was observed in tongue tissues. Therefore, PLE may have a beneficial effect on immune and inflammatory responses related to oral tumors and could be a promising natural therapeutic approach for preventing and treating oral cancer due its immunomodulatory activity [32].…”