Background: As a member of serine/threonine-protein kinase, Pololike kinase 1 (PLK1) plays crucial
roles during mitosis and also contributes to DNA damage response and repair. PLK1 is aberrantly expressed
in many types of tumor cells and increased levels of PLK1 are closely related to tumorigenesis and poor clinical
outcomes. Therefore, PLK1 is accepted as one of the potential targets for the discovery of novel anticancer
agents. The objective of this study was to assess the cytotoxic effects of a novel PLK1 inhibitor, RO3280,
against MCF-7, human breast cancer cells; HepG2, human hepatocellular carcinoma cells; and PC3, human
prostate cancer cells, as well as non-cancerous L929 fibroblast cells.
Methods: Antiproliferative activity of RO3280 was examined using the XTT assay. Flow cytometry assay was
performed to evaluate cell cycle distribution, apoptosis, multicaspase activity, mitochondrial membrane potential,
and DNA damage response. Apoptosis with fluorescence imaging studies was also examined.
Results: According to the results of XTT assay, although RO3280 displayed potent cytotoxicity in all treated
cancer cells, the most sensitive cell line was identified as MCF-7 cells that were selected for further studies. The
compound induced a cell cycle arrest in MCF-7 cells at G2/M phase and significantly induced apoptosis, multicaspase
activity, DNA damage response, and decreased mitochondrial membrane potential of MCF-7 cells.
Conclusion: Overall, RO3280 induces anticancer effects promoted mainly by DNA damage, cell cycle arrest,
and apoptosis in breast cancer cells. Further studies are needed to assess its usability as an anticancer agent with
specific cancer types.