MJ-66 induces malignant glioma cells G2/M phase arrest and mitotic catastrophe through regulation of cyclin B1/Cdk1 complexE

被引：21

作者：

Liu, Wei-Ting ^{[1
]}

Chen, Ching ^{[1
]}

Lu, I-Chen ^{[1
]}

Kuo, Sheng-Chu ^{[2
]}

Lee, Kuo-Hsiung ^{[3
,4
]}

Chen, Tai-Lin ^{[5
]}

Song, Ta-Shu ^{[5
]}

Lu, Yi-Liang ^{[5
]}

Gean, Po-Wu ^{[1
]}

Hour, Mann-Jen ^{[5
,6
]}

机构：

[1] Natl Cheng Kung Univ, Dept Pharmacol, Coll Med, Tainan 70101, Taiwan

[2] China Med Univ, Grad Inst Pharmaceut Chem, Taichung 40402, Taiwan

[3] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA

[4] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan

[5] China Med Univ, Sch Pharm, Taichung 40402, Taiwan

[6] China Med Univ Hosp, Taichung, Taiwan

来源：

NEUROPHARMACOLOGY | 2014年 / 86卷

关键词：

Malignant glioma; 2-(Naphthalene-1-yl)-6-pyrrolidinyl-4-quinazolinone; Mitotic catastrophe; G2/M arrest; Xenograft animal model; HUMAN GLIOBLASTOMA CELLS; ANTICANCER AGENTS; NUCLEAR-LOCALIZATION; TUMOR-CELLS; DNA-DAMAGE; DEATH; APOPTOSIS; DERIVATIVES; MECHANISMS; SURVIVAL;

D O I：

10.1016/j.neuropharm.2014.07.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Malignant gliomas are among the most devastating cancers as they are resistant to many kinds of treatment. Despite recent advances in the diagnosis and treatment, the prognosis of patients remains very poor and the development of new drug is urgently needed. Here, we report that a synthetic quinazolinone analog 2-(naphthalene-1-yl)-6-pyrrolidinyl-4-quinazolinone (MJ-66) induced glioma cell death. Immunofluorescence staining showed that MJ-66-induced cell death was associated with multinucleated phenotype and multipolar spindles that were typical characteristics of mitotic catastrophe. Flow cytometry analysis revealed that MJ-66 caused glioma cell cycle arrest at G2/M phase and increased the proportion of polyploidy cells. Western blotting indicated that the expression of cyclin B1, Cdk1 pY15 and Cdk1 increased after treatment with MJ-66. MJ-66 effectively inhibited tumor growth and induced apoptosis in the xenograft animal model of U87 human glioma cells. Together, these results suggest that MJ-66 inhibited malignant gliomas growth through inducing mitotic catastrophe by interference with G2/M cell cycle checkpoint which may open a new avenue for the treatment of malignant gliomas. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：219 / 227

页数：9

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