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dc.contributor.authorOmbredane, Alicia Simalie-
dc.contributor.authorAndrade, Laise Rodrigues de-
dc.contributor.authorBonadio, Raphael Severino-
dc.contributor.authorPinheiro, Willie Oliveira-
dc.contributor.authorAzevedo, Ricardo Bentes de-
dc.contributor.authorJoanitti, Graziella Anselmo-
dc.date.accessioned2021-06-08T13:54:23Z-
dc.date.available2021-06-08T13:54:23Z-
dc.date.issued2021-02-
dc.identifier.citationOMBREDANE, Alicia S. et al. Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival. Experimental Dermatology, v. 30, n. 5, p. 710-716, 2021. DOI: https://doi.org/10.1111/exd.14289.pt_BR
dc.identifier.urihttps://repositorio.unb.br/handle/10482/41115-
dc.language.isoInglêspt_BR
dc.publisherJohn Wiley & Sons Ltdpt_BR
dc.rightsAcesso Restritopt_BR
dc.titleMelittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survivalpt_BR
dc.typeArtigopt_BR
dc.subject.keyword5-fluorouracilpt_BR
dc.subject.keywordMelitinapt_BR
dc.subject.keywordPele - câncerpt_BR
dc.subject.keywordCarcinoma de células escamosaspt_BR
dc.identifier.doihttps://doi.org/10.1111/exd.14289pt_BR
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.14289pt_BR
dc.description.abstract1Combined 5-fluorouracil (5-FU) and melittin (MEL) is believed to enhance cytotoxic effects on skin squamous cell carcinoma (SCC). However, the rationale underlying cytotoxicity is fundamentally important for a proper design of combination chemotherapy, and to provide translational insights for future therapeutics in the dermatology field. The aim was to elucidate the effects of 5-FU/MEL combination on the viability, proliferation and key structures of human squamous cell carcinoma (A431). Morphology, plasma membrane, DNA, mitochondria, oxidative stress, cell viability, proliferation and cell death pathways were targeted for investigation by microscopy, MTT, trypan blue assay, flow cytometry and real-time cell analysis. 5-FU/MEL (0.25 µM/0.52 µM) enhanced the cytotoxic effect in A431 cells (74.46%, p < .001) after 72 h exposure, showing greater cytotoxic effect when compared to each isolated compound (45.55% 5-FU and 61.78% MEL). The results suggest that MEL induces plasma membrane alterations that culminate in a loss of integrity at subsequent times, sensitizing the cell to 5-FU action. DNA fragmentation, S and G2/M arrest, disruption of mitochondrial metabolism, and alterations in cell morphology culminated in proliferation blockage and apoptosis. 5-FU/MEL combination design optimizes the cytotoxic effects of each drug at lower concentrations, which may represent an innovative strategy for SCC therapy.pt_BR
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