Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival

Ombredane, Alicia Simalie; Andrade, Laise Rodrigues de; Bonadio, Raphael Severino; Pinheiro, Willie Oliveira; Azevedo, Ricardo Bentes de; Joanitti, Graziella Anselmo

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Campo DC	Valor	Idioma
dc.contributor.author	Ombredane, Alicia Simalie	-
dc.contributor.author	Andrade, Laise Rodrigues de	-
dc.contributor.author	Bonadio, Raphael Severino	-
dc.contributor.author	Pinheiro, Willie Oliveira	-
dc.contributor.author	Azevedo, Ricardo Bentes de	-
dc.contributor.author	Joanitti, Graziella Anselmo	-
dc.date.accessioned	2021-06-08T13:54:23Z	-
dc.date.available	2021-06-08T13:54:23Z	-
dc.date.issued	2021-02	-
dc.identifier.citation	OMBREDANE, 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.uri	https://repositorio.unb.br/handle/10482/41115	-
dc.language.iso	Inglês	pt_BR
dc.publisher	John Wiley & Sons Ltd	pt_BR
dc.rights	Acesso Restrito	pt_BR
dc.title	Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival	pt_BR
dc.type	Artigo	pt_BR
dc.subject.keyword	5-fluorouracil	pt_BR
dc.subject.keyword	Melitina	pt_BR
dc.subject.keyword	Pele - câncer	pt_BR
dc.subject.keyword	Carcinoma de células escamosas	pt_BR
dc.identifier.doi	https://doi.org/10.1111/exd.14289	pt_BR
dc.relation.publisherversion	https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.14289	pt_BR
dc.description.abstract1	Combined 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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