Alisertib (MLN8237), a selective Aurora-A kinase inhibitor, induces apoptosis in human tongue squamous cell carcinoma cell both in vitro and in vivo
- 312 Downloads
Aurora-A kinases are overexpressed in many cancer tissues and cells. Alisertib is an investigational, orally administered, selective, small-molecule Aurora-A kinase inhibitor with preclinical activity against a broad range of tumors. Our study was aimed to detect the effects of alisertib on human tongue squamous cell carcinoma (HTSCC). Treatment of a human tongue squamous cell carcinoma cell line, HSC-3, with alisertib to inhibition of Aurora-A kinases reduced proliferation and induced apoptosis, which was accompanied by activation of the ATM/Chk2/p53 pathway. In vivo, inhibition of Aurora-A kinases in established xenografted tumors decreased tumor size and weight. Kaplan-Meyer survival analysis demonstrated that the cumulative survival time of mice without Aurora-A kinases was significantly longer than those with Aurora-A kinases. Our data provide the basis for developing alisertib to treat human tongue squamous cell carcinoma.
KeywordsAlisertib Aurora-A Proliferation Apoptosis Survival rate
We appreciate the thoughtful advice of Yan Bai (China Medical University).
Conflict of interest
The authors declare no conflicts of interest
- 12.Kelly KR, Shea TC, Goy A, Berdeja JG, Reeder CB, McDonagh KT, et al. Phase I study of MLN8237-investigational Aurora A kinase inhibitor-in relapsed/refractory multiple myeloma, Non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs. 2013; [Epub ahead of print].Google Scholar
- 14.Dees EC, Cohen RB, von Mehren M, Stinchcombe TE, Liu H, Venkatakrishnan K, et al. Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Clin Cancer Res. 2012;18:4775–84.CrossRefPubMedGoogle Scholar
- 15.Qi W, Spier C, Liu X, Agarwal A, Cooke LS, Persky DO, et al. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment. Leuk Res. 2013;37:434–9.CrossRefPubMedGoogle Scholar
- 25.Sun H, Wang Y, Wang Z, Meng J, Qi Z, Yang G. Aurora-A controls cancer cell radio- and chemoresistance via ATM/Chk2-mediated DNA repair networks. Biochim Biophys Acta. 1843;2014:934–44.Google Scholar