Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas

Abstract

Malignant neoplasias constitute a public health issue, with around 600 thousand new cases of cancer projected to be diagnosed in Brazil between 2016 and 2017. In this context, breast cancer is the most common type in women, reaching around 28% of Brazilian women. Radiation therapy is a therapeutic modality commonly applied in cases of breast cancer in different stages. However, radioresistance, cutaneous radiation syndrome and the occurrence of new neoplasias in healthy cells are the main side effects of this practice. Therefore, the aim of this work was to assess the potential of resveratrol (RV) as a radiosensitizer radiomodifier on breast cancer cells of the lineage MCF-7. For this end, cells were initially treated with different RV doses (0, 10, 30 and 100μM) for 24 hours and then exposed to ionizing radiation (IR) (0, 1, 2 e 3 grays). The results show that the most cytotoxic treatment combination was 10μM and 3 grays, which were the doses chosen for the additional tests. Cellular death assessment through flow cytometry showed that, in 24 hours cell cultures after IR, necrosis/senescence seem to be related to cytotoxicity, besides the activation of extrinsic apoptosis. This phenomenon was clear when the high activity of caspases 3 and 8, and the low bax/bcl-2 ratio were observed. Tests involving oxidative metabolism show that RV and IR are effective together, causing great oxidative damage in DNA, proteins and cellular lipids, as well as diminishing the activity of the antioxidative enzymes dismutase (SOD) and catalase (CAT). The high expression of p53 indicates not to be primarily related to intrinsic apoptosis, but to be indeed related to the interruption of cell cycle in the S phase, which was observed in 72 hours cellular cultures after IR. Thus, the pro-oxidative condition established by the treatment combination, together with the high level of the p53 expression, allow us to suggest that the significant decrease of cellular proliferation in 72 hours cultures seems to be related to the irreversible growth interruption linked to necrosis/senescence, as well as apoptosis activation.