Evodiamine activates cellular apoptosis through suppressing PI3K/AKT and activating MAPK in glioma

被引：0

作者：

Feng ZHI ^{[1
,2
]}

Rong WANG ^{[2
]}

Dan-ni DENG ^{[2
]}

Nai-yuan SHAO ^{[1
]}

Yuan XU ^{[2
]}

Lian XUE ^{[2
]}

Ya PENG ^{[1
]}

Ya-tian LIU ^{[3
]}

机构：

[1] Department of Neurosurgery,The First People's Hospital of Changzhou

[2] Modern Medical Research Center,The Third Affiliated Hospital of Soochow University

[3] Department of Radiation Oncology,Jiangsu Cancer Hospital,Jiangsu Institute of Cancer Research,Nanjing Medical University Affiliated Cancer Hospital

来源：

中国药理学与毒理学杂志 | 2018年 / 32卷 / 04期

关键词：

evodiamine; apoptosis; protein kinase B; mitogen-activated protein kinase; glioma;

D O I：

暂无

中图分类号：

R285.5 [中药实验药理];

学科分类号：

1008 ;

摘要：

OBJECTIVE Glioblastoma multiforme（GBM） is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine（Evo） on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L;) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species（ROS） production was detected using dichlorofluorescein diacetate（DCFH-DA） staining.The changes in mitochondrial mem.brane potential（MMP） were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species（ROS） production and mitochondrial membrane potential（MMP） disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation（p38 and JNK,but not ERK） to regulate apoptotic proteins（Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP）.CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.

引用

页码：342 / 343

页数：2