Background:
As a member of serine/threonine-protein kinase, Polo‐like 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 is
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. We also examined
apoptosis with fluorescence imaging studies.
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.
Targeting of lactate dehydrogenase C dysregulates the cell cycle and sensitizes breast cancer cells to DNA damage response targeted therapy.
