THERAPEUTIC EFFECTIVENESS OF THE PAN-AURORA KINASE INHIBITOR REVERSINE ON SKBR3 BREAST CANCER CELL LINE.

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

Institution: Universidade Federal de Goiás

“The aurora kinases are serine/threonine kinases that function as key regulators of mitosis. Abnormal expression or activation of these proteins leads to the development of cancer, and inhibiting their enzyme activity is potentially a good targeted cancer therapy. However, few data have been obtained on breast cancer. In the current study, we identified the cellular viability and pro-apoptotic effects of the aurora kinase inhibitor REVERSINE on SKBR3 breast cancer cell line. For the experiments SKBR3 cells (epithelial breast cancer cell lines), and MCF10A (the normal breast epithelial cell line) were used to determine the effects of REVERSINE. SKBR3 and MCF10A cells were plated into 6-well tissue culture plates in duplicate and grown in medium individually. The cells were treated with medium containing REVERSINE at 5, 10, 25, 50, and 100µM. After incubation for 24, 48, and 72h, apoptosis and cellular viability were determined. Our results showed that the treatment with REVERSINE reduced cell viability and induce apoptosis in a dose-dependent manner. In 24 hours for example, the percentage of cellular viability of MCF10A cells over the control cells (100%) was 98.2%(5µM), 91.2% (10µM), 88.8%(25µM), 63.1%(50µM), and 54.6%(100µM), and the percentage of cellular viability of SKBR3 cells was 82.3%(5µM), 68.9%(25µM), 37.3%(50µM), and 19.1%(100µM). These results indicate that the cytotoxic effect of REVERSINE is much lower in normal MCF10A cells than in malignant cell line SKBR3 (p?0,05%). For apoptosis we found that the expression level of cleaved caspase-9 was significantly increased after REVERSINE treatment, which subsequently activated caspase-3 in SKBR3 cells (p?0,05%). This study suggests that REVERSINE may represent a promising therapeutic agent for targeted therapy in breast cancer. More studies are needed to reveal the underlying mechanisms for the anticancer effect of REVERSINE and to verify the efficacy and safety in the treatment of breast cancer.

Supported by the CNPq research group EPICOL.

Keywords: Breast cancer; REVERSINE; Aurora kinase; Apoptosis.”

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