The Aurora kinases inhibitor VE-465 is a novel treatment for glioblastoma multiforme.

Abstract

Glioblastoma multiforme (GBM) is one of the most common and aggressive types of primary brain tumor. After complete surgical resection combined with radiation and chemotherapy, approximately 10% of patients survive for more than 5 years. Therefore, a novel therapy for GBM is needed. Aurora-A (AURKA) plays important roles in cell cycle regulation, such as centrosome maturation, chromatic separation, bipolar spindle assembly, and mitotic entry. To investigate the effects of AURKA inhibition, three GBM cell lines, including GBM 8401, GBM 8901, and U87-MG cells, were treated with the AURKA inhibitor VE-465. Sensitivities to VE-465, as indicated by 50% inhibitory concentration values for GBM 8401, GBM 8901, and U87-MG cells, were 6, 25, and 19 nM, respectively. Additionally, colony formation of GBM 8401 and GBM 8901 cells was decreased after treatment with the VE-465. VE-465 treatment increased polyploidy and p53 protein expression, and inhibited cell growth in a caspase-independent manner. Taken together, these results suggest that the inhibition of AURKA by a small-molecule inhibitor may have potential to serve as a novel therapeutic approach for GBM.

• Authors: Pei-Ying Lee, Chi-Long Chen, Zhong-Zhe Lin, Ann-Lii Cheng, Edmund I-Tsuen Chen, Jacqueline Whang-Peng, Chi-Ying F Huang
• Journal: Oncology (Oncology) Vol. 84 Issue 6 Pg. 326-35 ( 2013) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 23636005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents
• Piperazines
• Tumor Suppressor Protein p53
• tozasertib
• AURKA protein, human
• Aurora Kinase A
• Aurora Kinases
• Protein Serine-Threonine Kinases
• Caspase 3
• Caspase 8
• Caspase 9

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Aurora Kinase A
• Aurora Kinases
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Count
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Glioblastoma (drug therapy, enzymology)
• Humans
• Inhibitory Concentration 50
• Piperazines (pharmacology, therapeutic use)
• Polyploidy
• Protein Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
• Tumor Stem Cell Assay
• Tumor Suppressor Protein p53 (metabolism)