TY - JOUR
T1 - The aurora kinases inhibitor VE-465 is a novel treatment for glioblastoma multiforme
AU - Lee, Pei Ying
AU - Chen, Chi Long
AU - Lin, Zhong Zhe
AU - Cheng, Ann Lii
AU - Chen, Edmund I.Tsuen
AU - Whang-Peng, Jacqueline
AU - Huang, Chi Ying F.
N1 - Publisher Copyright:
© 2013 S. Karger AG, Basel.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Brain tumor
KW - Glioblastoma multiforme
KW - VE-465
UR - http://www.scopus.com/inward/record.url?scp=84876800051&partnerID=8YFLogxK
U2 - 10.1159/000347021
DO - 10.1159/000347021
M3 - Article
AN - SCOPUS:84876800051
SN - 0030-2414
VL - 84
SP - 326
EP - 335
JO - Oncology (Switzerland)
JF - Oncology (Switzerland)
IS - 6
ER -