title: Aristolochic acid induces apoptosis of human umbilical vein endothelial cells in vitro by suppressing PI3K/Akt signaling pathway.
abstract: OBJECTIVE
  To investigate whether aristolochic acid (AA) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) in vitro and the underlying mechanism.
  
  
  METHODS
  HUVECs were treated with AA (5, 10 or 20 μg/mL) for 12, 24 and 48 h. Cell viabilities were determined with MTT assay. Hoechst 33258 staining and flow cytometry were used to examine the apoptosis of HUVECs. Western blotting was used to evaluate Akt phosphorylation. Bcl-2 and Bax levels were measured using Western blotting and RT-PCR assays.
  
  
  RESULTS
  Treatment of HUVECs with AA significantly decreased the cell viabilities in dose- and time-dependent manners. Morphological changes of apoptosis were observed in AA-treated cells. AA inhibited Akt activation, which was attenuated by pretreatment of the cells with LY294002 (20 μmol/L) or wortmannin (50 nmol/L). Furthermore, AA reduced Bcl-2 levels and increased Bax levels.
  
  
  CONCLUSIONS
  AA induces apoptosis of HUVECs in vitro via the PI3K/Akt signaling pathway and by modulating the ratio Bcl-2 and Bax.
authors.affiliation: Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang, China. fengjiangmin2007@hotmail.com
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Jiang-min
authors.initials: JM
authors.lastname: Feng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D034341:Aristolochic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034341:Aristolochic Acids; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt