Background:Dysregulation of the cell cycle is one of the main causes of melanomagenesis. Genomewide
studies showed that the expression of Aurora -A and -B significantly has been upregulated in melanoma.
However, there is no FDA approved drug targeting aurora kinases in the treatment of melanoma. In addition, the
development of resistance to chemotherapeutic agents in the treatment of melanoma and, as a result, the relapse
due to heterogeneous cell groups in patients is a second phenomenon that causes treatment failure. Therefore,
there is an urgent need for therapeutic alternatives targeting both melanoma and Melanoma Cancer Stem Cells
(MCSCs) in treatments. At this stage, cell cycle regulators become promising targets.Objective:In this study, we aimed to identify the effects of Aurora kinase inhibitor CCT137690 on the
cytotoxicity, apoptosis, cell cycle, migration, and colony formation and expression changes of genes related to
proliferation, cell death and cell cycle in melanoma and melanoma cancer stem cell. In addition, we investigated
the apoptotic and cytostatic effects of CCT137690 in normal fibroblast cells.Methods:We evaluated the cytotoxic effect of CCT137690 in MCSCs, NM2C5 referring as melanoma model
cells and WI-38 cells by using the WST-1 test. The effect of CCT137690 on apoptosis was detected via Annexin
V and JC-1 method; on cell cycle progression by cell cycle test; on gene expression by using RT-PCR, on
migration activity by wound healing assay and clonal growth by clonogenic assay in NM2C5 cells and MCSCs.
The effects of CCT137690 in WI-38, referring as healthy fibroblast cell, were assessed through Annexin V and
cell cycle method.Results:CCT137690 was determined to have a cytotoxic and apoptotic effect in MCSCs and melanoma. It
caused polyploidy and cell cycle arrest at the G2/M phase in MCSCs and melanoma cells. The significant
decrease in the expression of MMP2, MMP7, MMP10, CCNB1, IRAK1, PLK2 genes, and the increase in the
expression of PTEN, CASP7, p53 genes were detected.Conclusion:Aurora kinases inhibitor CCT137690 displays promising anticancer activity in melanoma and
especially melanoma cancer stem cells. The effect of CCT137690 on melanoma and MCSC may provide a new
approach to treatment protocols.