In vitro attenuation of classic metastatic melanoma‑related features by highly diluted natural complexes: Molecular and functional analyses

Gonçalves,Jenifer Pendiuk; Potrich,Francine Bittencourt; Ferreira Dos Santos,Maria Luiza; Costa Gagosian,Viviana Stephanie; Rodrigues Rossi,Gustavo; Jacomasso,Thiago; Mendes,Aline; Bonciani Nader,Helena; Brochado Winnischofer,Sheila Maria; Trindade,Edvaldo S.; Camargo De Oliveira,Carolina

doi:10.3892/ijo.2019.4846

In vitro attenuation of classic metastatic melanoma‑related features by highly diluted natural complexes: Molecular and functional analyses

Authors:
- Jenifer Pendiuk Gonçalves
- Francine Bittencourt Potrich
- Maria Luiza Ferreira Dos Santos
- Viviana Stephanie Costa Gagosian
- Gustavo Rodrigues Rossi
- Thiago Jacomasso
- Aline Mendes
- Helena Bonciani Nader
- Sheila Maria Brochado Winnischofer
- Edvaldo S. Trindade
- Carolina Camargo De Oliveira
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Affiliations: Laboratory of Inflammatory and Neoplastic Cells/Laboratory of Sulfated Polysaccharides Investigation, Cell Biology Department, Section of Biological Sciences, Federal University of Paraná, CEP 81530‑980 Curitiba‑PR, Brazil, Biochemistry Department, Federal University of São Paulo, São Paulo ‑ SP 04023‑062, Brazil, Biochemistry and Molecular Biology Department, Section of Biological Sciences, Federal University of Paraná, CEP 81530‑980 Curitiba‑PR, Brazil
Published online on: July 22, 2019 https://doi.org/10.3892/ijo.2019.4846
Pages: 721-732

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Abstract

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.

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