title: Andrographolide induces apoptosis of C6 glioma cells via the ERK-p53-caspase 7-PARP pathway.
abstract: BACKGROUND
  Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo.
  
  
  METHODS
  Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model.
  
  
  CONCLUSIONS
  In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No. 7, Zhongshan South Road, Zhongzheng District, Taipei City 100, Taiwan.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei 10051, Taiwan.
authors.forename: Seu-Mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei 10051, Taiwan.
authors.forename: Jhih-Pu
authors.initials: JP
authors.lastname: Syu
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei City 114, Taiwan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei 10051, Taiwan.
authors.forename: Sheng-De
authors.initials: SD
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya South Road, Banqiao District, New Taipei City 220, Taiwan.
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Peng
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No. 7, Zhongshan South Road, Zhongzheng District, Taipei City 100, Taiwan.
authors.forename: Meng-Fai
authors.initials: MF
authors.lastname: Kuo
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei 10051, Taiwan.
authors.forename: Hsiu-Ni
authors.initials: HN
authors.lastname: Kung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053179:Caspase 7 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D004224:Diterpenes; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C030419:andrographolide; D048051:p38 Mitogen-Activated Protein Kinases; C505524:Casp7 protein, mouse; D053179:Caspase 7