Eupatilin inhibits EGF-induced JB6 cell transformation by targeting PI3K

Abstract

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play fundamental roles in regulation of multiple signaling pathways, including cell proliferation, survival and cell cycle. Increasing evidence has shown that abnormal activation of PI3K pathway contributes to tumorigenesis and progression of various malignant tumors. Therefore, it is an attractive target of chemoprevention and chemotherapy. Eupatilin, a natural flavone compound extracted from Artemisia vulgaris, has antitumor and anti-inflammation efficacy. However, the direct target(s) of eupatilin in cancer chemoprevention are still elusive. In the present study, we reported eupatilin suppressed JB6 cell proliferation and its EGF-induced colony formation. Eupatilin attenuated phosphorylation of PI3K downstream signaling molecules. Downregulation of cyclin D1 expression and arresting in G1 phase were induced through eupatilin treatment. Furthermore, we found it could bind to the p110α, a catalytic subunit of PI3K, by computational docking methods. Pull down assay outcomes also verified the binding of eupatilin with PI3K. Taken together, our results suggest that epatilin is a potential chemopreventive agent in inhibition of skin cell transformation by targeting PI3K.

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

“…This is in line with the diverse therapeutic function of eupatilin in various diseases through transinteraction. Another study also suggests that eupatilin targets the AKT signaling pathway in cancer cells, causing cell cycle arrest [27]. Treatment with eupatilin in the xenograft mouse model for esophageal cancer inhibits the activity of AKT and ERK1/2 in tissues [9].…”

Eupatilin inhibits the proliferation of human esophageal cancer TE1 cells by targeting the Akt‑GSK3β and MAPK/ERK signaling cascades

“…2 and 3). Our previous study demonstrated that eupatilin induced cell cycle arrest at the G 0 /G 1 phase by inhibiting the activity of cyclin D1 in EGF-treated JB6 cells (24). However, G 2 /M arrest of the cell cycle has been observed in eupatilin-treated human endometrial carcinoma Hec1A cells (37).…”

“…Thus, there is an urgent need to identify more useful methods that can prevent or treat the malignant cancer. Eupatilin, a flavone compound, has potential anticancer activity (6,24). It has been reported that eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways (25).…”

“…It has been reported that eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways (25). Epatilin is a potential chemopreventive agent in inhibition of skin cell transformation by targeting PI3K, and is independent of the ERK-related signaling pathway (ERK1/2, RSK2 and CREB) (24). However, to the best of our knowledge, no study has explored the effect of eupatilin on human esophageal cancer cells.…”