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

Authors Wang R, Deng D, Shao N, Xu Y, Xue L, Peng Y, Liu Y, Zhi F

Received 26 October 2017

Accepted for publication 18 January 2018

Published 2 March 2018 Volume 2018:11 Pages 1183—1192


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Carlos E Vigil

Rong Wang,1,2,* Danni Deng,2,* Naiyuan Shao,1 Yuan Xu,2 Lian Xue,2 Ya Peng,1 Yatian Liu,3 Feng Zhi1,2

1Department of Neurosurgery, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, China; 2Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China; 3Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, China

*These authors contributed equally to this work

Background: 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, developing new agents to treat GBM is important.
Aim: This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved.
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 phosphorylation (p38 and JNK, but not ERK) to regulate apoptotic proteins (Bax, Bcl-2, Cytochrome c, Caspase-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.

Keywords: evodiamine, apoptosis, Akt, MAPK, glioma

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