Evaluation of melatonin treatment in primary culture of canine mammary tumors.
Mammary neoplasias are the most common tumors observed in female dogs. Identification of these tumors is valuable in order to identify beneficial therapeutic agents as alternative treatments for this tumor type. Oral administration of melatonin appears to exert an oncostatic effect on mammary neoplasia and may have a possible mechanism of action through its interaction with estrogen receptors on epithelial cells. Hence, we analyzed the potential therapeutic value of melatonin in tumors that are estrogen-dependent or -independent, and established a relationship of its action with the expression of the melatonin receptors MT1 and MT2. Furthermore, we analyzed the rate of cell proliferation and apoptosis after treatment with melatonin. Cell cultures were performed using 10 canine mammary tumor fragments and were divided into estrogen receptor (ER)-positive and ER-negative tumors. The results showed that both ER-positive and ER-negative tumors had decreased cell viability and proliferation after treatment with melatonin (p<0.05), although treatment was more effective in the ER-positive tumors. Analysis of the relative expression of the MT1 and MT2 genes by quantitative PCR was performed and the data were compared with the expression of ER in 24 canine mammary tumors and the cellular response to melatonin in 10 samples. MT1 was overexpressed in ER-positive tumors (p<0.05), whereas MT2 was not expressed. Furthermore, melatonin treatment in ER-positive tumors showed an efficient oncostatic effect by inhibiting cell viability and proliferation and inducing apoptosis. These results suggest that melatonin decreased neoplastic mammary cell proliferation and viability and induced apoptosis, with greater efficacy in ER-positive tumors that have a high expression of melatonin receptor MT1. This is a strong evidence for the use of melatonin as a therapeutic agent for estrogen-dependent canine mammary tumors.
Post-graduate Program in Genetics, São Paulo State University (UNESP), São José do Rio Preto, SP, Brazil.
Juliana Ramos
JR
Lopes
Post-graduate Program in Genetics, São Paulo State University (UNESP), São José do Rio Preto, SP, Brazil.
Larissa Bazela
LB
Maschio
Post-graduate Program in Genetics, São Paulo State University (UNESP), São José do Rio Preto, SP, Brazil.
Bruna Victorasso
BV
Jardim-Perassi
Laboratory of Molecular Research in Cancer (LIMC), São José do Rio Preto, SP, Brazil.
Marina Gobbe
MG
Moschetta
Post-graduate Program in Genetics, São Paulo State University (UNESP), São José do Rio Preto, SP, Brazil.
Lívia Carvalho
LC
Ferreira
Laboratory of Molecular Research in Cancer (LIMC), São José do Rio Preto, SP, Brazil.
Gustavo Rodrigues
GR
Martins
Post-graduate Program in Genetics, São Paulo State University (UNESP), São José do Rio Preto, SP, Brazil.
Gabriela Bottaro
GB
Gelaleti
Laboratory of Molecular Research in Cancer (LIMC), São José do Rio Preto, SP, Brazil.
Debora Aparecida Pires
DA
De Campos Zuccari
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D061251:Primary Cell Culture; D044122:Receptor, Melatonin, MT1 / Q000235:genetics / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin