title: Icaritin causes sustained ERK1/2 activation and induces apoptosis in human endometrial cancer cells.
abstract: Icaritin, a compound from Epimedium Genus, has selective estrogen receptor (ER) modulating activities, and possess anti-tumor activity. Here, we examined icaritin effect on cell growth of human endometrial cancer Hec1A cells and found that icaritin potently inhibited proliferation of Hec1A cells. Icaritin-inhibited cell growth was associated with increased levels of p21 and p27 expression and reduced cyclinD1 and cdk 4 expression. Icaritin also induced cell apoptosis accompanied by activation of caspases as evidenced by the cleavage of endogenous substrate Poly (ADP-ribose) polymerase (PARP) and cytochrome c release, which was abrogated by pretreatment with the pan-caspase inhibitor z-VAD-fmk. Icaritin treatment also induced expression of pro-apoptotic protein Bax with a concomitant decrease of Bcl-2 expression. Furthermore, icaritin induced sustained phosphorylation of extracellular signal-regulated kinase1/2 (the MAPK/ ERK1/2) in Hec1A cells and U0126, a specific MAP kinase kinase (MEK1/2) inhibitor, blocked the ERK1/2 activation by icaritin and abolished the icaritin-induced growth inhibition and apoptosis. Our results demonstrated that icaritin induced sustained ERK 1/2 activation and inhibited growth of endometrial cancer Hec1A cells, and provided a rational for preclinical and clinical evaluation of icaritin for endometrial cancer therapy.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Tong
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Xue-Qi
authors.initials: XQ
authors.lastname: Fu
authors.forename: Shu-Tao
authors.initials: ST
authors.lastname: Qi
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020169:Caspases; C499403:icaritin