Evaluation of Melatonin Effect on Human Breast Cancer Stem Cells Using a Threedimensional Growth Method of Mammospheres.
BACKGROUND
The high rates of women&amp;#039;s death from breast cancer occur due to acquired resistance by patients to certain treatments, enabling the recurrence and/or tumor growth, invasion and metastasis. It has been demonstrated that the presence of cancer stem cells in human tumors, as responsible for recurrence and resistance to therapy. Studies have identified OCT4 as responsible for self-renewal and maintenance of pluripotency of stem cells. Thus, it is interesting to study potential drugs that target this specific population in breast cancer. Melatonin, appears to have oncostatic effects on cancer cells, however, little is known about its therapeutic effect on cancer stem cells.


OBJECTIVE
Evaluate the viability and the expression of OCT4 in breast cancer stem cells, MCF-7 and MDA-MB- 231, after melatonin treatment.


METHODS
The cells were grown in a 3-dimensional model of mammospheres, representing the breast cancer stem cell population and treated or not with melatonin. The cell viability of mammospheres were evaluated by MTT assay and the OCT4 expression, a cancer stem cells marker, was verified by immunocitochemistry.


RESULTS
Our results demonstrated that the melatonin treatment decreased the cell viability of MCF-7 and MDAMB- 231 mammospheres. Furthermore, it was observed that in both cell lines, the expression of OCT4 was decreased in melatonin-treated cells compared to the control group.


CONCLUSIONS
This fact suggests that melatonin is effective against breast cancer stem cells inhibiting the cell viability via OCT 4. Based on that, we believe that melatonin has a high potential to be used as an alternative treatment for breast cancer.
Postgraduate program in Genetics, Universidade Estadual Paulista, UNESP/IBILCE, São José do Rio Preto, SP, Brazil. Cristovão Colombo, 2265, Zip Code: 15054-000, São José do Rio Preto, SP. Brazil.
Juliana Ramos
JR
Lopes
Laboratory of Molecular Research in Cancer (LIMC), Department of Molecular Biology, FAMERP, Brazil. Brigadeiro Faria Lima, 5416, Zip Code: 15090-000, São José do Rio Preto, SP. Brazil.
Mayume
M
da Silva Kavagutti
Laboratory of Molecular Research in Cancer (LIMC), Department of Molecular Biology, FAMERP, Brazil. Brigadeiro Faria Lima, 5416, Zip Code: 15090-000, São José do Rio Preto, SP. Brazil.
Felipe Arthur Faustino
FAF
de Medeiros
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
DAP
de Campos Zuccari
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001940:Breast / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008550:Melatonin / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000032:analysis
D000970:Antineoplastic Agents; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D008550:Melatonin
Mammospheres; OCT4; breast cancer; immunocytochemistry and three-dimensional; melatonin