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Type: Artigo de Periódico
Title: 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
Authors: Aranha, Elenn Suzany Pereira
Portilho, Adrhyann Jullyanne de Sousa
Sousa, Leilane Bentes de
Silva, Emerson Lucena da
Mesquita, Felipe Pantoja
Rocha, Waldireny C.
Silva, Felipe Moura Araújo da
Lima, Emerson Silva
Alves, Ana Paula Negreiros Nunes
Koolen, Hector Henrique Ferreira
Montenegro, Raquel Carvalho
Vasconcellos, Marne Carvalho de
Keywords: Apoptose;Apoptosis;Melanoma;Metaloproteinase 9 da Matriz;Matrix Metalloproteinase 9;Proteínas Quinases Ativadas por Mitógeno;Mitogen-Activated Protein Kinases
Issue Date: 2021
Publisher: Journal of Ethnopharmacology
Citation: ARANHA, Elenn Suzany Pereira et al. 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling. Journal of Ethnopharmacology, v. 267, 113605, mar. 2021. Disponível em: Acesso em: 13/12/2021.
Abstract: Ethnopharmacological relevance: 22β-hydroxytingenone (22-HTG) is a quinonemethide triterpene isolated from Salacia impressifolia (Miers) A. C. Smith (family Celastraceae), which has been used in traditional medicine to treat a variety of diseases, including dengue, renal infections, rheumatism and cancer. However, the anticancer effects of 22-HTG and the underlying molecular mechanisms in melanoma cells have not yet been elucidated. Aim of the study: The present study investigated apoptosis induction and antimetastatic potencial of 22-HTG in SK-MEL-28 human melanoma cells. Materials and methods: First, the in vitro cytotoxic activity of 22-HTG in cultured cancer cells was evaluated. Then, cell viability was determined using the trypan blue assay in melanoma cells (SK-MEL-28), which was followed by cell cycle, annexin V-FITC/propidium iodide assays (Annexin/PI), as well as assays to evaluate mitochondrial membrane potential, production of reactive oxygen species (ROS) using flow cytometry. Fluorescence microscopy using acridine orange/ethidium bromide (AO/BE) staining was also performed. RT-qPCR was carried out to evaluate the expression of BRAF, NRAS, and KRAS genes. The anti-invasiveness potential of 22-HTG was evaluated in a three-dimensional (3D) model of reconstructed human skin. Results: 22-HTG reduced viability of SK-MEL-28 cells and caused morphological changes, as cell shrinkage, chromatin condensation, and nuclear fragmentation. Furthermore, 22-HTG caused apoptosis, which was demonstrated by increased staining with AO/BE and Annexin/PI. The apoptosis may have been caused by mitochondrial instability without the involvement of ROS production. The expression of BRAF, NRAS, and KRAS, which are important biomarkers in melanoma development, was reduced by the 22-HTG treatment. In the reconstructed skin model, 22-HTG was able to decrease the invasion capacity of melanoma cells in the dermis.
ISSN: 0378-8741
Appears in Collections:PPGF - Artigos publicados em revistas científica

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