CYTOTOXIC EFFECTS OF THE AURORA KINASE INHIBITOR DANUSERTIB IN HUMAN BREAST CANCER CELL LINES.

Bianca Dantas Vieira, Andressa Oliveira Pereira, Fabrício Gomes de Freitas, Luiz Fabio Falcão, Mariana Sousa Rodrigues, Edlaine Faria de Moura Villela, Fábio Morato de Oliveira

I nstitution: Universidade Federal de Goiás – Regional Jataí

“In the current study, we identified the cytotoxic effects of the aurora kinase inhibitor danusertib on MDA-MB-231 breast cancer cell line. For the experiments, MDA-MB-231 cells and MCF10A (the normal breast epithelial cell line) were used to determine the effects of danusertib. Both cell types were plated into 6-well tissue culture plates in duplicate and grown in medium individually. The cells were treated with medium containing danusertib at 0.01, 0.1, 1.0 and 5.0µM. After incubation for 24, 48, and 72h, cellular viability, cell cycle and apoptosis were determined. We observed that the reduced cell viability and capacity of apoptosis induction was considered a dose dependent. Thus, when MCF10A cells were treated with danusertib the percentage of cellular viability over the control cells, (24h of exposure) was 94.3%(0.01µM), 88.9%(0.1µM), 77.5%(1.0µM), and 64.2%(5.0µM). The percentage of live MDA-MB-231 cells over the control cells was 73.1%(0.01µM), 69.3%(0.1µM), 53.6%(1.0µM), and 31.2%(0.01µM). The cytotoxic effect of danusertib was more expressive on MDA-MB-231 cells than in normal cell line (MCF10A) (p?0,05%). We also observed that the exposure of MCF10A and MDAMB-231 cells with danusertib arrested cells in G2 /M phase in a concentration-dependent way. The percentage of MCF10A and MDA-MB-231 cells in G2 /M phase was 23.5% and 31.6%, respectively. The number of apoptotic cells was 11.2% and 12.3% in MCF10A and MDA-MB-231 cells treated with DMSO, respectively. In MCF10A cells treated with danusertib at 1.0 and 5.0 µM (24h), the total percentages of apoptotic cells were 17.6% and 29.5%, respectively. For MDAMB-231 cells using the same concentrations and 24 hours of exposure, the total percentages of apoptotic cells were 37,6% and 58.3%, respectively. These results indicate that danusertib may represent a promising anticancer drug. However, more studies are necessary elucidate the safety of danusertib in the treatment of human breast cancer.

Supported by the CNPq research group EPICOL

Keywords: Breast cancer; danusertib; Aurora kinase; Cytotoxicity “