Abstract

Abstract The oral squamous cell carcinoma (OSCC) is the eighth most prevalent malignant neoplasm and representing an important health problem worldwide. OSCCs have a highly variable clinical course, and due to its late diagnostic in advanced stages, the overall survival rate is less than 50% in 5 years. Despite the advances and last recent discoveries, the prognosis of this disease is still unpredictable. The search for new therapeutic strategies of OSCC is still needed to improve patient survival. From this point of view, oscc treatment and adjuvant methods represent a promising and challenging field for researchers. In the last few years, the use of some types of complementary medicines, such as phytotherapeutic products, has significantly increased among cancer patients. Recently, a phytotherapeutic compound, Polypodium Leucotomos (PL), was particularly introduced on the market for the treatment of inflammatory changes and other skin diseases caused by UV radiation, due to its anti-inflammatory, anti-oxidant and immunomodulatory properties. It is possible that PL also demonstrates antitumor action, and therefore seems a plausible target for further investigation regarding its therapeutic potential on oral cancer. The present study has characterized the biological effects of the extract of PL on proliferation, migration and invasion of oral cancer cell lines; and investigated the antitumor potential of PL in vivo, by treating oral tumors chemically induced on the tongue of Balb/C mice. Our results showed that oral cancer cells proliferations measured by MTT assay has decreased up to 60% and 78% for a period of 48hrs PL treatment for the SSC9 and LN1 cells, respectively. The scratch assay did not demonstrate a significant reduction on the migration potential these cells. As for the invasion assay, we verified that both lineages, but mainly LN1, a more aggressive oscc cell line, diminish its breach capacity, after previous incubation with PL (p<0.01). We further investigated whether PL extract would have any role in protecting the cellular DNA of the damages caused by UV radiation, often associated with cancer. The comet assay data showed that normal primary gingival fibroblasts previously treated with PL, and then submitted to UVR, had a reduction on DNA damage in about 40%, compared to the fibroblasts non treated (p<0.05). Our preliminary in vivo assays suggest that PL extract has an antitumor activity. Majority of animals with 4NQO-induced tongue tumor recovered weight after 6 weeks treatment, with significant reduction of tumor size and decreased Ki67 positivity in the injured oral tissue, compared the mice not treated with PL extract. Altogether, our results demonstrated, for the first time, the potential of the extract Polypodium Leucotomos as an effective phytotherapeutic agent for prevention and/or adjuvant treatment of oral cancer. Citation Format: Pammela A. Borges, Gabriela S. Teixeira, Nathalia N. Pantarotto, Luan Oenning, Liliane O. Marinho, Lucilene Lopes, Eduardo J. Caldeira, Pablo A. Salvador, Ricardo D. Colleta, Clóvis A. Pinto, Gustavo Simões Augusto, Taize M. Augusto, Carine E. Oliveira, Nilva K. Cervigne. Antitumor promoting activity of the phytotherapic Polypodium leucotomos in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2680.

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