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

Abstract

Xiaowei Fei,1,2 Ji Wang,1 Chen Chen,1 Boyun Ding,1 Xiaojun Fu,1 Wenjing Chen,1 Chongwu Wang,1 Ruxiang Xu11Institute 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 ChinaPurpose: 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  

Keywords

• Eupatilin
• glioma
• proliferation
• cell cycle
• migration
• invasion