title: Wortmannin inhibits proliferation and induces apoptosis of MCF-7 breast cancer cells.
abstract: OBJECTIVE
  The present study aimed to explore the effects of wortmannin in the proliferation and apoptosis of human breast cancer MCF-7 cells.
  
  
  METHODS
  The authors treated cells with 0, 1, 6.25, 12.5, 25, and 50 nM wortmannin for 24, 48, and 72 hours. Inhibition of proliferation was measured by cell counting kit-8 assay (CCK8). Apoptosis was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry. Additionally, expression of proteins involved in the PI3K pathway, specifically total Akt, phosphorylated Akt (p-Akt), and NF-kappaB was detected by Western blotting following 24 hours of wortmannin exposure.
  
  
  RESULTS
  Higher doses (6.25, 12.5, 25, and 50 nM) of wortmannin significantly inhibited proliferation of MCF-7 cells after 24, 48, and 72 hours of exposure compared with control MCF-7 cells incubated with DMSO alone in DMEM (p < 0.05). This inhibition increased with concentration and duration of treatment. Similarly, wortmannin at 6.25, 12.5, 25, and 50 nM concentrations significantly increased apoptosis of MCF-7 cells following 24 hours of exposure (p < 0.05). Western blotting revealed that increasing concentrations of wortmannin (6.25, 12.5, 25, and 50 nM, 24 hours) increasingly reduced expression of p-Akt and NF-kappaB; however, expression of total Akt was unaffected at any concentration of wortmannin.
  
  
  CONCLUSIONS
  Wortmannin inhibits proliferation and induces apoptosis of MCF-7 cells in a dose and time-dependent manner, likely through down-regulation of PI3K/Akt signaling and NF-kappaB protein expression.
authors.affiliation: Department of Vascular and Endocrine Surgery, The Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: J
authors.initials: J
authors.lastname: Yun
authors.forename: Y G
authors.initials: YG
authors.lastname: Lv
authors.forename: Q
authors.initials: Q
authors.lastname: Yao
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: Y P
authors.initials: YP
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Yi
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin