Título:	Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
Autor(es):	Ombredane, Alicia Simalie Andrade, Laise Rodrigues de Bonadio, Raphael Severino Pinheiro, Willie Oliveira Azevedo, Ricardo Bentes de Joanitti, Graziella Anselmo
Assunto:	5-fluorouracil Melitina Pele - câncer Carcinoma de células escamosas
Data de publicação:	Fev-2021
Editora:	John Wiley & Sons Ltd
Referência:	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.
Abstract:	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.
DOI:	https://doi.org/10.1111/exd.14289
Versão da editora:	https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.14289
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