Verification of agomelatine in comparison to melatonin as a therapeutic agent in breast cancer

• Grant number: 17/18832-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2018
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Debora Aparecida Pires de Campos Zuccari
• Grantee: Amabile Oficiati de Carnevale Galeti
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Breast cancer is the most prevalent neoplasm in women worldwide. In 2016, it was estimated that 57,960 new cases occurred in Brazil. This cancer presents a high mortality rate and morbidity, so it is interesting to discover new therapeutic agents. Several studies have found that melatonin, the main hormone synthesized by the pineal gland, regulates the circadian cycle and plays an important role in the control of breast tumorigenesis. The deregulation of the circadian cycle is associated to changes in cellular proliferation and to the development of psychotic disorders, like major depression and affective disorder. For the treatment of these disorders, recent studies recommend the use of agomelatine, a melatonin analog, which has chronobiotic, anxiolytic and antidepressant effects and accelerates the resynchronization of circadian rhythms. Melatonin and agomelatine may exert their functions by binding to membrane receptors coupled to protein G, MT1 and MT2. This way agomelatine may also have activity in breast cancer cells, thus creating a promising pathway for its use as adjuvant therapeutic agent for this type of neoplasia. Therefore, considering the success of studies performed with melatonin, the investigation of the relationship between this melatonergic analogue with the pathogenesis of breast cancer is fundamental. Therefore, the aim of the present study is first, verify the expression of the MT1 receptor in breast cancer cell lines (MCF-7 and MDA-MB-231), and then investigate and compare the action of melatonin and agomelatine by cell viability, clonogenic survival and cell migration assays. The results obtained in this study could verify the potential benefit of the use of melatonin and agomelatine as therapeutic agents in the treatment of breast cancer. (AU)