22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling.

Autor: Aranha ESP; Faculty of Pharmaceutical Sciences, Post Graduate Program in Biodiversity and Biotechnology of the Amazon (Bionorte), Federal University of Amazonas, Manaus, Amazonas, 69080-900, Brazil. Electronic address: elenn_suzany@yahoo.com.br., Portilho AJS; Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil. Electronic address: dryportilhoo@gmail.com., Bentes de Sousa L; Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus, Amazonas, 69080-900, Brazil. Electronic address: leilane.bentes@gmail.com., da Silva EL; Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil. Electronic address: lucenaemerson@hotmail.com., Mesquita FP; Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil. Electronic address: felipe_mesquita05@hotmail.com., Rocha WC; Health and Biotechnology Institute, Federal University of Amazonas, Coari, Amazonas, 69460-000, Brazil. Electronic address: wal2002@gmail.com., Araújo da Silva FM; Department of Chemistry, Federal University of Amazonas, Manaus, Amazonas, 69080-900, Brazil. Electronic address: felipesaquarema@bol.com.br., Lima ES; Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus, Amazonas, 69080-900, Brazil. Electronic address: eslima75@gmail.com., Alves APNN; Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil. Electronic address: ananegreirosnunes@gmail.com., Koolen HHF; Metabolomics and Mass Spectrometry Research Group, Amazonas State University (UEA), Manaus, Amazonas, 690065-130, Brazil. Electronic address: hectorkoolen@gmail.com., Montenegro RC; Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil. Electronic address: rcm.montenegro@gmail.com., Vasconcellos MC; Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus, Amazonas, 69080-900, Brazil. Electronic address: marnevasconcellos@yahoo.com.br.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2021 Mar 01; Vol. 267, pp. 113605. Date of Electronic Publication: 2020 Nov 21.
DOI: 10.1016/j.jep.2020.113605
Abstrakt: 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.
Conclusions: Our data indicate that 22-HTG has anti-tumorigenic properties against melanoma cells through the induction of cell cycle arrest, apoptosis and inhibition of invasiveness potential, as observed in the 3D model. As such, the results provide new insights for future work on the utilization of 22-HTG in malignant melanoma treatment.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: