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.

• Authors: Feng Li, Ya Tao, Yan Qiao, Ke Li, Yanan Jiang, Chang Cao, Shuxin Ren, Xiaobin Chang, Xiaona Wang, Yanhong Wang, Yifei Xie, Ziming Dong, Jimin Zhao, Kangdong Liu
• Journal: International journal of oncology (Int J Oncol) Vol. 49 Issue 3 Pg. 1148-54 (Sep 2016) ISSN: 1791-2423 [Electronic] Greece
• PMID: 27573489 (Publication Type: Journal Article)

Chemical References

• Flavonoids
• eupatilin
• Epidermal Growth Factor
• Phosphatidylinositol 3-Kinases
• 1-phosphatidylinositol 3-kinase p110 subunit, mouse
• Class I Phosphatidylinositol 3-Kinases

Topics

• Animals
• Cell Line
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (drug effects)
• Class I Phosphatidylinositol 3-Kinases (metabolism)
• Epidermal Growth Factor (pharmacology)
• Flavonoids (pharmacology)
• Gene Expression Regulation
• Mice
• Molecular Docking Simulation
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)