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

Abstract

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.

Eupatilin Promotes Cell Death by Calcium Influx through ER-Mitochondria Axis with SERPINB11 Inhibition in Epithelial Ovarian Cancer

“…Eupatilin also activates the apoptotic pathway mediated by the cleavage of caspase-3 in gastric cancer cells, similar to the results verified in ovarian cancer cells in this study [23]. Moreover, cell cycle arrest is one of the routes of eupatilin-induced anticancer effects in gastric cancer and glioma, as demonstrated in ovarian cancer cells [24,25]. Eupatilin also triggered apoptosis by elevating p53 and p21 in agreement with the Bax, Bcl-2, and Parp regulations in human gastric cancer (AGS) cells [23].…”

Eupatilin Impacts on the Progression of Colon Cancer by Mitochondria Dysfunction and Oxidative Stress

“…For instance, eupatilin inhibits endometrial cancer cell growth by inducing G2/M phase cell cycle arrest and regulating ERK and AKT phosphorylation [13]. Eupatilin also suppresses proliferation, migration, and invasion, and it induces cell cycle arrest at the G1/S phase in glioma cells [11,29]. In esophageal cancer cells, eupatilin suppresses cell growth by inhibiting AKT and ERK phosphorylation, as well as by inducing G1 phase arrest [10].…”

Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies

“…One study screened a library of 273 kinase inhibitors and identified thiazovivin (a pyrimidine-based non-selective ROCK inhibitor) as a significant hit (63). It is also interesting to note that the plant flavanoid, eupatilin, which was highlighted as a potential therapeutic for CEP290 -related retinal dystrophy (11) and has been used to treat the Rpgrip1l -/- mouse (64), has an indirect effect on actin cytoskeleton remodelling that is mediated by CEP290 (65). Several other screens have identified other biological targets for the restoration of cilia, for example a screen to identify drugs that restore cilia expression in cancer cells identified 118 compounds, many of which affect levels of cAMP, calcium or other ions (66).…”