Format

Send to

Choose Destination
EBioMedicine. 2017 Dec;26:100-111. doi: 10.1016/j.ebiom.2017.10.030. Epub 2017 Nov 3.

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

Author information

1
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
2
Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, PR China; Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, PR China.
3
Department of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.
4
Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China.
5
Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, PR China; Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, PR China. Electronic address: Weililx@163.com.
6
Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China; Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China. Electronic address: haidanliu@csu.edu.cn.

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.

KEYWORDS:

Aurora B; Deguelin; Esophageal squamous cell carcinoma; Mitosis

PMID:
29129699
PMCID:
PMC5832566
DOI:
10.1016/j.ebiom.2017.10.030
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center