Atividade de fagócitos do colostro humano co-cultivados com células tumorais de mama modulados pela associação de melatonina e interleucina-10

Abstract

As one of the main public health problems in the world, breast cancer takes first place among the most incident types of tumors. It is considered that besides being the most important food for the development of the newborn, breastfeeding acts as a protective factor against breast cancer, and the bioactive and immunological components of colostrum are important resources to establish this relationship. The improvement of alternative treatments to fight cancer has been fundamental to the development of new study guidelines such as immunotherapy. Several studies sustain that the ability to modulate the immune system and direct it against various pathologies, including tumors, has proven to be promising in relation to traditional forms of treatment, and can be established through the measurement of cytokines, such as interleukin10 (IL-10). However, several evaluations on IL-10 reveal its conflicting and paradoxical role during oncogenesis, since this cytokine seems to act both in tumor progression and regression. Melatonin is a hormone with antioxidant and anti-inflammatory properties that has tumor killing activities. In this scenario, the association of this hormone with IL-10 could provide promising results by stimulating the antitumor effects of this cytokine, improving immunotherapeutic methods against cancer. In this sense, the aim of this study is to verify the influence of melatonin modulation associated with IL-10 on the activity of human colostrum phagocytes co-cultured with breast tumor cells (MCF-7). For this purpose, six human colostrum samples were used from which mononuclear cells (MN) were obtained. MCF-7 cells were cultured in nutrient medium and then incubated in an incubator (37°C - 5% CO2) for 24 hours with MN cells to assess viability in the presence of melatonin (100 ng.ml-1) and IL-10 (100 ng.ml-1), and a control group was established for each treatment. Viability indices were determined by counting live and dead cells in fluorescence microscopy using the Acridine Orange method. Statistical ANOVA tests followed by Dunnet's multiple comparisons tests were employed to check for significant differences (p<0.05). It was observed that viability of MN cells was not compromised by melatonin, but was elevated by IL-10 independent of association with melatonin. MCF-7 cells treated with melatonin showed elevation in death rates, but the presence of IL-10 safeguarded the survival of these cells, even when associated with melatonin. Similarly, co-culture of MN and MCF-7 cells had viability reduced by melatonin, but elevated during the presence of IL-10. These results indicate that the cytokine possesses pro-tumor properties by preventing melatonin from killing MCF-7 cells. Although more studies are needed, this association can be considered an important therapeutic target against cancer.