title: Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin.
abstract: BACKGROUND
  Baicalin, a flavone present in Scutellaria baicalensis Georgi, inhibits the growth of human leukemia and myeloma cells through induction of apoptosis.
  
  
  METHODS
  The present study was undertaken to ascertain whether cultured Burkitt lymphoma cells undergo apoptosis when treated with baicalin. Growth rates were measured using MTT and colony formation assays, and induction of apoptosis was quantified using Annexin V and DNA fragmentation assays. Mechanisms underlying observed growth suppression were examined using Western blotting.
  
  
  RESULTS
  Treatment of CA46 Burkitt lymphoma cells with baicalin for 48 h markedly decreased the rate of cell proliferation; an IC50 value of 10 μM was obtained. Colony formation was almost fully suppressed at 10 μM baicalin. CA46 cells underwent apoptosis in response to baicalin treatment as evidenced by an increase in the percentage of cells stainable with Annexin V, by increased DNA fragmentation, and by activation of the intrinsic (mitochondrial) pathway for cell death as characterized by increased expression of the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase. Additionally, baicalin was found to down-regulate anti-apoptotic and up-regulate apoptotic components of the phosphatidylinositide-3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway.
  
  
  CONCLUSIONS
  The concentrations at which baicalin altered expression of components of the PI3K/Akt pathway in CA46 cells were comparable to those that suppressed growth and induced apoptosis, supporting the hypothesis that the observed growth-inhibitory and apoptosis-inducing actions of baicalin in these cells are mediated by down-regulation of this pathway.
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350000 Fujian, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Jianda
authors.initials: J
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Tiannan
authors.initials: T
authors.lastname: Wei
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; C038044:baicalin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt