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

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 futur...

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Main Authors: Ombredane, Alicia Simalie, Andrade, Laise Rodrigues de, Bonadio, Raphael Severino, Pinheiro, Willie Oliveira, Azevedo, Ricardo Bentes de, Joanitti, Graziella Anselmo
Format: Artigo
Language: Inglês
Published: John Wiley & Sons Ltd 2021
Subjects:
5-fluorouracil
Melitina
Pele - câncer
Carcinoma de células escamosas
Online Access: https://repositorio.unb.br/handle/10482/41115
https://doi.org/10.1111/exd.14289
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spelling ir-10482-411152021-06-08T13:54:35Z 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 5-fluorouracil Melitina Pele - câncer Carcinoma de células escamosas 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. 2021-06-08T13:54:23Z 2021-06-08T13:54:23Z 2021-02 Artigo 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. https://repositorio.unb.br/handle/10482/41115 https://doi.org/10.1111/exd.14289 Inglês https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.14289 Acesso Restrito John Wiley & Sons Ltd
institution REPOSITORIO UNB
collection REPOSITORIO UNB
language Inglês
topic 5-fluorouracil
Melitina
Pele - câncer
Carcinoma de células escamosas
spellingShingle 5-fluorouracil
Melitina
Pele - câncer
Carcinoma de células escamosas
Ombredane, Alicia Simalie
Andrade, Laise Rodrigues de
Bonadio, Raphael Severino
Pinheiro, Willie Oliveira
Azevedo, Ricardo Bentes de
Joanitti, Graziella Anselmo
Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
description 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.
format Artigo
author Ombredane, Alicia Simalie
Andrade, Laise Rodrigues de
Bonadio, Raphael Severino
Pinheiro, Willie Oliveira
Azevedo, Ricardo Bentes de
Joanitti, Graziella Anselmo
author_sort Ombredane, Alicia Simalie
title Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
title_short Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
title_full Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
title_fullStr Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
title_full_unstemmed Melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
title_sort melittin sensitizes skin squamous carcinoma cells to 5-fluorouracil by affecting cell proliferation and survival
publisher John Wiley & Sons Ltd
publishDate 2021
url https://repositorio.unb.br/handle/10482/41115
https://doi.org/10.1111/exd.14289
_version_ 1710449616429776896
score 13.657419

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