Proceedings of Oncobiology Symposiums
Proceedings of XIV Oncobiology Symposium

Introduction and objective: Cancer is one of the leading causes of death in the world. In Brazil, there is an incidence of about 66,000 breast cancer diagnoses per year - the most common cancer among women. Breast cancer occurs due to genetic mutations that interfere with breast cells, furthermore, the presence or absence of hormone receptors and growth factors influence the type and treatment of cancer. Currently, through early diagnosis, it is possible to reduce the incidence of mortality. However, the treatment is still uncomfortable and with many side effects. In order to search for new drug candidates with less adverse effects, we tested a series of dibutylfsphofonates. Phosphonates and their derivatives are currently on the market as antivirals and for osteoporosis treatment. Previous studies have shown that bisphosphonates reduce the chance of bone cancer metastasis. Therefore, the goal of this study is to evaluate the effect and efficacy of a series of compounds in order to select future drug candidates for the treatment of breast cancer.
Material and methods: Breast cancer cell lines MCF-7 and MDA-MB231 were maintained in DMEM culture medium supplemented with 10% fetal bovine serum. The viability assay with MTT for the screening of the compounds was carried out at a concentration of 100 μM for 24 hours. To evaluate the dose-response and calculate the IC50, Neutral Red and MTT assay were performed with concentrations ranging from 1.562 to 100 μM. The clonogenic assay was performed with varied ranges of concentration according to the IC50 obtained from each compound in order to evaluate the formation of the colonies. The assay with spheroids was performed at concentrations ranging from 1.562 to 100 μM and then its viability was analyzed using resazurin and acid phosphatase.
Results and conclusion: The screening showed excellent cytotoxic activity of five compounds on MCF-7, so all experiments were performed exclusively on this cell line. Through the dose-response curve, the calculated IC50 values ranged from 6 μM to 23 μM. We observed an influence of compounds in reducing the formation of colonies. In the analysis of the 3D cells, it was possible to observe a disintegration of the spheroids when treated after their formation. Also, spheroids did not form when treated on the same day of plating. The experiments carried out so far indicate an excellent antitumor activity of the compounds, but toxicological experiments with normal breast cells and experiments to elucidate the mechanism of action of the compounds are still necessary.