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Eupatilin inhibits glioma proliferation, migration, and invasion by arresting cell cycle at G1/S phase and disrupting the cytoskeletal structure

Authors Fei X, Wang J, Chen C, Ding B, Fu X, Chen W, Wang C, Xu R

Received 8 March 2019

Accepted for publication 30 April 2019

Published 24 May 2019 Volume 2019:11 Pages 4781—4796

DOI https://doi.org/10.2147/CMAR.S207257

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Chien-Feng Li


Xiaowei Fei,1,2 Ji Wang,1 Chen Chen,1 Boyun Ding,1 Xiaojun Fu,1 Wenjing Chen,1 Chongwu Wang,1 Ruxiang Xu1

1Institute of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Beijing 10000, People’s Republic of China; 2Department of Physiology, Dalian Medical University, Dalian 116044, People’s Republic of China

Purpose: Eupatilin is a pharmacologically active flavonoid extracted from Asteraceae argyi that has been identified as having antitumor effects. Gliomas are the most common intracranial malignant tumors and are associated with high mortality and a poor postoperative prognosis. There are few studies on the therapeutic effects of eupatilin on glioma. Therefore, we explored the efficacy and the underlying molecular mechanism of eupatilin on glioma.
Methods: The effect of eupatilin on cell proliferation and viability was detected using Cell Counting Kit-8 assays. Cell migration was analyzed with a scratch wound healing assay and invasion was analyzed using transwell assays.
Results: We found that eupatilin significantly inhibits the viability and proliferation of glioma cells by arresting the cell cycle at the G1/S phase. In addition, eupatilin disrupts the structure of the cytoskeleton and affects F-actin depolymerization via the “P-LIMK”/cofilin pathway, thereby inhibiting the migration of glioma. We also found that eupatilin inhibits the invasion of gliomas. The underlying mechanism may be related to the destruction of epithelial–mesenchymal transition, with eupatilin also affecting the RECK/matrix metalloproteinase pathway. However, we did not observe the proapoptotic effect of eupatilin on glioma, which is inconsistent with other studies. Finally, we observed a significant inhibitory effect of eupatilin on U87MG glioma in xenograft nude mice.
Conclusion: Eupatilin inhibits the viability and proliferation of glioma cells, attenuates the migration and invasion, and inhibits tumor growth in vivo, but does not promote apoptosis. Therefore, due to the poor clinical efficacy of drug treatment of glioma and high drug resistance, the emergence of eupatilin brings a new dawn for glioma patients.

Keywords: eupatilin, glioma, proliferation, cell cycle, migration, invasion
 

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