In vitro attenuation of classic metastatic melanoma‑related features by highly diluted natural complexes: Molecular and functional analyses
Autor: | Thiago Jacomasso, Helena B. Nader, Francine Bittencourt Potrich, Sheila M.B. Winnischofer, Gustavo Rodrigues Rossi, Carolina Camargo de Oliveira, Edvaldo S. Trindade, Aline Mendes, Jenifer Pendiuk Gonçalves, Viviana Stephanie Costa Gagosian, Maria Luiza Ferreira dos Santos |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research BALB 3T3 Cells Skin Neoplasms Angiogenesis Metastasis Mice 03 medical and health sciences 0302 clinical medicine Antigens CD Cell Movement In vivo Cell Line Tumor Cell Adhesion medicine Animals Humans Neoplasm Metastasis Clonogenic assay Melanoma Cell Proliferation Tumor microenvironment biology Plant Extracts Integrin beta1 CD44 Plants Cell cycle Cadherins medicine.disease Gene Expression Regulation Neoplastic Hyaluronan Receptors 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Drug Screening Assays Antitumor |
Zdroj: | International Journal of Oncology. |
ISSN: | 1791-2423 1019-6439 |
DOI: | 10.3892/ijo.2019.4846 |
Popis: | Metastasis is responsible for the majority of deaths among patients with malignant melanoma. Despite recent advances, the majority of current and modern therapies are ineffective and/or financially unfeasible. Thus, in this study, we investigated two low‑cost highly‑diluted natural complexes (HDNCs) that have been shown to be effective against malignant melanoma in a murine model in vivo. The aim of this study was to determine the mechanisms through which these HDNCs directly affect melanoma cells, either alone or in an artificial tumor microenvironment, suppressing the metastatic phenotype, thus explaining previous in vivo effects. For this purpose, HDNC in vitro treatments of B16‑F10 melanoma cells, alone or in co‑culture with Balb/3T3 fibroblasts, were carried out. Molecular biology techniques and standard functional assays were used to assess the changes in molecule expression and in cell behaviors related to the metastatic phenotype. Melanoma progression features were found to be regulated by HDNCs. Molecules related to cell adhesion (N‑cadherin, β1‑integrin and CD44), and migration, extracellular matrix remodeling and angiogenesis were modulated. The cell migratory, invasive and clonogenic capacities were reduced by the HDNCs. No loss of cell proliferation or viability were observed. On the whole, the findings of this study indicate that HDNCs directly reprogram, molecularly and functionally, melanoma cells in vitro, modulating their metastatic phenotype. Such findings are likely to be responsible for the attenuation of tumor growth and lung colonization previously observed in vivo. |
Databáze: | OpenAIRE |
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