title: 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: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Feng
authors: F
authors: Li
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Ya
authors: Y
authors: Tao
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Yan
authors: Y
authors: Qiao
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Ke
authors: K
authors: Li
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Yanan
authors: Y
authors: Jiang
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Chang
authors: C
authors: Cao
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Shuxin
authors: S
authors: Ren
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Xiaobin
authors: X
authors: Chang
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Xiaona
authors: X
authors: Wang
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Yanhong
authors: Y
authors: Wang
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Yifei
authors: Y
authors: Xie
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Ziming
authors: Z
authors: Dong
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Jimin
authors: J
authors: Zhao
authors: Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
authors: Kangdong
authors: K
authors: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation; D051379:Mice; D062105:Molecular Docking Simulation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; C045325:eupatilin; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases