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Anticancer Agents Med Chem. 2019 Jun 18. doi: 10.2174/1871520619666190618162828. [Epub ahead of print]

RO3280, A Novel PLK1 Inhibitor, Suppressed Proliferation of MCF-7 Breast Cancer Cells Through Induction of Cell Cycle Arrest at G2/M Point.

Author information

1
Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas. Turkey.
2
Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara. Turkey.

Abstract

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 has 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 provides anticancer effects promoted mainly by DNA damage, cell cycle arrest, and apoptosis in breast cancer cells. It has merit for further studies to assess its usability as an anticancer agent with specific cancer types.

KEYWORDS:

Apoptosis; DNA damage; PLK inhibition; RO3280; cell cycle; cytotoxicity

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