title: [Evodiamine induces extrinsic and intrinsic apoptosis of ovarian cancer cells via the mitogen-activated protein kinase/phosphatidylinositol-3-kinase/protein kinase B signaling pathways].
abstract: OBJECTIVE
  To explore the effects of evodiamine on ovarian cancer cells and the mechanisms underlying such effects.
  
  
  METHODS
  Human. ovarian cancer cells HO-8910PM were treated with evodiamine at 0, 1.25, 2.5, and 5 μM for 1-4 d. 3-(4,5-Dimethiylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the growth inhibition rate of evodiamine-treated HO-8910PM cells. The cell cycle was observed via propidium iodide (PI) staining. Apoptosis induction was assessed via Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining assay. To verify the mechanism of apoptosis, caspase-dependent apoptotic pathway-related protein was detected by Western blot analysis. The expression levels of mitogen-activated protein kinase (MAPK) and/or phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway-related proteins were also investigated.
  
  
  RESULTS
  Evodiamine significantly inhibited the proliferation of HO-8910PM cells in a dose- and time-dependent manner. Evodiamine induced G2/M arrest with an increase of cyclin B1 level, and promoted cell apoptosis with a decrease of B cell lymphoma/lewkmia-2 (Bcl-2) and an increase of Bcl-2-associated X protein (Bax) level. In addition, evodiamine treatment led to the activation of caspase-8, caspase-9, and caspase-3 and the cleavage of poly (ADP-ribose)-polymerase (PARP). Evodiamine targeted the MAPK and/or PI3K/Akt pathways by reducing the expression and activity of PI3K, Akt, and extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the activity of p38 MAPK.
  
  
  CONCLUSIONS
  Evodiamine can inhibit the growth of ovarian cancer cells by G2/M arrest and intrinsic and extrinsic apoptosis. In addition, evodiamine-induced PI3K/Akt, ERK1/2 MAPK, and p38 MAPK signaling may be involved in cell death.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wei
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Jin
authors.forename: Zipei
authors.initials: Z
authors.lastname: Cao
authors.forename: Wenlu
authors.initials: W
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal; D032086:Evodia / Q000737:chemistry*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D011799:Quinazolines; C049639:evodiamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases