Abstract
Background: Cancer-associated fibroblast (CAFs) are the most abundant cells in the tumor microenvironment, able to secrete growth factors and act on tumor progression. Melatonin is associated with several mechanisms of action with oncostatics and oncoprotectors effects, and also participate in the reduction of synthesis of surrounding fibroblasts and endothelial cells in breast cancer.
Objective: The objectives of this study were to determine the effectiveness of melatonin in cell viability and expression of proteins involved in angiogenesis and inflammation in triplenegative mammary tumor cell line (MDA-MB-231) and in co-culture with CAFs.
Method: Cell viability was measured by MTT assay and the protein expression was evaluated by Membrane Antibody Array after melatonin treatment.
Results: Melatonin treatment (1 mM) for 48 hours reduced the cell viability of MDA-MB-231, CAFs and co-culture (p < 0.05). The semi-quantitative protein analysis showed that when monoculture of tumor cells were compared with co-culture of CAFs, there was a regulation of angiogenic and inflammatory proteins (p < 0.05). Melatonin treatment also leads a differential expression of angiogenic and inflammatory proteins in both monoculture and co-culture of tumor cells and CAFs (p < 0.05).
Conclusion: The influence of CAFs under the tumor microenvironment was confirmed, increasing the malignancy of the tumor. In addition, melatonin is effective in both monoculture and co-culture, regulating angiogenic and inflammatory proteins that contribute to tumor progression. This study show an overview of melatonin ability in regulating angiogenic and inflammatory proteins, and opens the way for exploration of each individual protein in further studies.
Keywords: Breast cancer, melatonin, microenvironment, angiogenesis, inflammation, co-culture.
Anti-Cancer Agents in Medicinal Chemistry
Title:Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts
Volume: 16 Issue: 11
Author(s): Larissa B. Maschio-Signorini, Gabriela B. Gelaleti, Marina G. Moschetta, Thaiz F. Borin, Bruna V. Jardim-Perassi, Juliana R. Lopes, Jéssica Z. Lacerda, Rosimeire A. Roela, Newton A. Bordin, Lizandra A. Corrêa, Jessica P. Cardoso and Debora Aparecida Pires de Campos Zuccari
Affiliation:
Keywords: Breast cancer, melatonin, microenvironment, angiogenesis, inflammation, co-culture.
Abstract: Background: Cancer-associated fibroblast (CAFs) are the most abundant cells in the tumor microenvironment, able to secrete growth factors and act on tumor progression. Melatonin is associated with several mechanisms of action with oncostatics and oncoprotectors effects, and also participate in the reduction of synthesis of surrounding fibroblasts and endothelial cells in breast cancer.
Objective: The objectives of this study were to determine the effectiveness of melatonin in cell viability and expression of proteins involved in angiogenesis and inflammation in triplenegative mammary tumor cell line (MDA-MB-231) and in co-culture with CAFs.
Method: Cell viability was measured by MTT assay and the protein expression was evaluated by Membrane Antibody Array after melatonin treatment.
Results: Melatonin treatment (1 mM) for 48 hours reduced the cell viability of MDA-MB-231, CAFs and co-culture (p < 0.05). The semi-quantitative protein analysis showed that when monoculture of tumor cells were compared with co-culture of CAFs, there was a regulation of angiogenic and inflammatory proteins (p < 0.05). Melatonin treatment also leads a differential expression of angiogenic and inflammatory proteins in both monoculture and co-culture of tumor cells and CAFs (p < 0.05).
Conclusion: The influence of CAFs under the tumor microenvironment was confirmed, increasing the malignancy of the tumor. In addition, melatonin is effective in both monoculture and co-culture, regulating angiogenic and inflammatory proteins that contribute to tumor progression. This study show an overview of melatonin ability in regulating angiogenic and inflammatory proteins, and opens the way for exploration of each individual protein in further studies.
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Maschio-Signorini B. Larissa, Gelaleti B. Gabriela, Moschetta G. Marina, Borin F. Thaiz, Jardim-Perassi V. Bruna, Lopes R. Juliana, Lacerda Z. Jéssica, Roela A. Rosimeire, Bordin A. Newton, Corrêa A. Lizandra, Cardoso P. Jessica and Zuccari Aparecida Pires de Campos Debora, Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (11) . https://dx.doi.org/10.2174/1871520616666160422105920
DOI https://dx.doi.org/10.2174/1871520616666160422105920 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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