title: Dihydroartemisin inhibits glioma invasiveness via a ROS to P53 to β-catenin signaling.
abstract: Dihydroartemisinin(DHA) is the active metabolic derivative of artemisinin. DHA has potential therapeutic effects on glioma but the detailed mechanism is unclear. In this study, we investigated the role and the underlying mechanisms of DHA in its inhibition of glioma cells. U87 cells are wild-type p53 glioblastoma cells and U251 cells contain mutant p53. DHA inhibited the proliferation, migration and invasion of glioma cells in a dose-dependent manner. DHA promoted reactive oxygen species production and activated p53 in two glioma cell lines, U87 and U251. In U87 cells, DHA significantly up-regulated the expression of p-β-catenin (S45) and inhibited EGFR, β-catenin, p-β-catenin (Y333) and matrix metalloprotease7/9 activity. In U251 cells, DHA significantly up-regulated p-β-catenin (S45), p-β-catenin (Y333) and EGFR, but the expression of β-cateninwas unchanged. We also found that DHA and sh-β-catenin prevented the proliferation of U87 and U251 cells in vivo. In conclusion, DHA inhibited the migration and invasion of human glioma cells with different types of p53 via different pathways.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Zhongyou
authors.initials: Z
authors.lastname: Que
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China. Electronic address: neurosurgery_sj@163.com.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C039060:artenimol; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9
keywords: Dihydroartemisinin; Dihydroartemisinin (PubChem CID:456410); Glioma; Invasion; Migration; P53; β-Catenin