Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts.
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.



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.



Cell viability was measured by MTT assay and the protein expression was evaluated by Membrane Antibody Array after melatonin treatment.



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).



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.
Larissa B
LB
Maschio-Signorini
Gabriela B
GB
Gelaleti
Marina G
MG
Moschetta
Thaiz F
TF
Borin
Bruna V
BV
Jardim-Perassi
Juliana R
JR
Lopes
Jéssica Z
JZ
Lacerda
Rosimeire A
RA
Roela
Newton A
NA
Bordin
Lizandra A
LA
Corrêa
Jessica P
JP
Cardoso
Laboratory of Molecular Research in Cancer (LIMC), Faculty of Medicine of São José do Rio Preto (FAMERP), Brigadeiro Faria Lima, 5416, Vila São Pedro, São José do Rio Preto (SP), Brazil.
Debora Aparecida Pires de Campos
DA
Zuccari
D000072645:Cancer-Associated Fibroblasts / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008550:Melatonin / Q000737:chemistry / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D008550:Melatonin