YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects.

Abstract

PURPOSE:

Polo-like kinase 4 (PLK4), a member of the polo-like kinase family, plays several important roles in mitotic regulation, including centrosome duplication, spindle formation, and cytokinesis. PLK4 overexpression is frequently detected in many human cancers, including ovarian cancer, and the inhibition of PLK4 activity results in cancer cell mitotic arrest and apoptosis. Therefore, PLK4 might be a valid therapeutic target for antitumor therapy. In the present study, we aimed to determine if YLZ-F5, a potent small-molecule inhibitor of PLK4, inhibits ovarian cancer cell growth.

METHODS AND RESULTS:

MTT assay showed that YLZ-F5 inhibited ovarian cancer cell proliferation in a concentration- and time-dependent manner. The results of colony formation assays were consistent with those of the MTT assay results. In addition, YLZ-F5 induced ovarian cancer cell apoptosis that was associated with activation of caspase-3/caspase-9. Moreover, YLZ-F5 caused aberrant in centriole duplication that was associated with the inhibition of PLK4 phosphorylation. Notably, we showed that YLZ-F5 promoted the accumulation of ovarian cancer cells with mitotic defects (> 4 N DNA content) in a concentration-dependent manner. Furthermore, YLZ-F5 markedly inhibited the migration of A2780 cells.

CONCLUSION:

Taken together, these findings suggest that YLZ-F5 is a potential drug candidate for human ovarian cancer.

• Authors: Yongxia Zhu, Zhihao Liu, Yanling Qu, Jun Zeng, Meiqin Yang, Xiaoyi Li, Zhaodi Wang, Junxiang Su, Xueqin Wang, Luoting Yu, Yue Wang
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 86 Issue 1 Pg. 33-43 (07 2020) ISSN: 1432-0843 [Electronic] Germany
• PMID: 32519033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Indazoles
• Protein Kinase Inhibitors
• PLK4 protein, human
• Protein Serine-Threonine Kinases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Centrioles (drug effects)
• Female
• Humans
• Indazoles (pharmacology)
• Mitosis (drug effects)
• Ovarian Neoplasms (drug therapy, pathology)
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism)