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