Elsevier

EBioMedicine

Volume 26, December 2017, Pages 100-111
EBioMedicine

Research Paper
Deguelin, an Aurora B Kinase Inhibitor, Exhibits Potent Anti-Tumor Effect in Human Esophageal Squamous Cell Carcinoma

https://doi.org/10.1016/j.ebiom.2017.10.030Get rights and content
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Highlights

  • Aurora B is overexpressed in human esophageal squamous cell carcinoma (ESCC), high levels of Aurora B protein are associated with a worse overall survival rate in ESCC patients.

  • Deguelin inhibits the growth of ESCC cells both in vitro and in vivo.

  • Deguelin potently inhibits in vitro Aurora B kinase activity and is docked into the ATP-binding pocket of Aurora B. Deguelin acts as an effective Aurora B inhibitor.

Abstract

Aurora B kinase has emerged as a key regulator of mitosis and deregulation of Aurora B activity is closely related to the development and progression of human cancers. In the present study, we found that Aurora B is overexpressed in human esophageal squamous cell carcinoma (ESCC), high levels of Aurora B protein were associated with a worse overall survival rate in ESCC patients. Depleting of Aurora B blunted the malignant phenotypes in ESCC cells. Importantly, we demonstrated that a natural compound, deguelin, has a profound anti-tumor effect on ESCC via inhibiting Aurora B activity. Deguelin potently inhibited in vitro Aurora B kinase activity. The in silico docking study further indicated that deguelin was docked into the ATP-binding pocket of Aurora B. Inhibition of Aurora B activity attenuated growth of ESCC cells, resulted in G2/M cell cycle arrest, polyploidy cells formation, and apoptosis induction. Knocking down of Aurora B decreased the sensitivity of ESCC cells to deguelin. The in vivo results showed that deguelin blocked the phosphorylation of histone H3 and inhibited the growth of ESCC tumor xenografts. Overall, we identified deguelin as an effective Aurora B inhibitor, which deserves further studies in other animal models and ESCC treatment.

Abbreviations

ESCC
esophageal squamous cell carcinoma;
RNase A
ribonuclease A
OS
overall survival
shRNA
short nairpin RNA
DMSO
dimethyl sulphoxide

Keywords

Esophageal squamous cell carcinoma
Deguelin
Aurora B
Mitosis

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1

These authors contributed equally to this work.