title: Kaempferol Downregulates Insulin-like Growth Factor-I Receptor and ErbB3 Signaling in HT-29 Human Colon Cancer Cells.
abstract: BACKGROUND
  Novel dietary agents for colon cancer prevention and therapy are desired. Kaempferol, a flavonol, has been reported to possess anticancer activity. However, little is known about the molecular mechanisms of the anticancer effects of kaempferol. The aim of this study was to determine the inhibitory effect of kaempferol on growth factor-induced proliferation and to elucidate its underlying mechanisms in the HT-29 human colon cancer cell line.
  
  
  METHODS
  To assess the effects of kaempferol and/or growth factors [insulin-like growth factor (IGF)-I and heregulin (HRG)-β], cells were cultured with or without 60 μmol/L kaempferol and/or 10 nmol/L IGF-I or 20 μg/L HRG-β. Cell proliferation, DNA synthesis, and apoptosis were determined by a cell viability assay, a [(3)H]thymidine incorporation assay, and Annexin-V staining, respectively. Western blotting, immunoprecipitation, and an in vitro kinase assay were conducted to evaluate expression and activation of various signaling molecules involved in the IGF-I receptor (IGF-IR) and ErbB3 signaling pathways.
  
  
  RESULTS
  IGF-I and HRG-β stimulated HT-29 cell growth but did not abrogate kaempferol-induced growth inhibition and apoptosis. Kaempferol reduced IGF-II secretion, HRG expression and phosphorylation of Akt and extracellular signal-regulated kinase (ERK)-1/2. Kaempferol reduced IGF-I- and HRG-β-induced phosphorylation of the IGF-IR and ErbB3, their association with p85, and phosphatidylinositol 3-kinase (PI3K) activity. Additionally, kaempferol inhibited IGF-I- and HRG-β-induced phosphorylation of Akt and ERK-1/2.
  
  
  CONCLUSIONS
  The results demonstrate that kaempferol downregulates activation of PI3K/Akt and ERK-1/2 pathways by inhibiting IGF-IR and ErbB3 signaling in HT-29 cells. We suggest that kaempferol could be a useful chemopreventive agent against colon cancer.
authors.affiliation: Department of Food Science and Nutrition, Dongseo University, Busan, Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Korea ; WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Korea.
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Korea.
authors.forename: Gyoo Taik
authors.initials: GT
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Korea ; Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Korea.
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
keywords: ErbB3; HT-29 human colon cancer; Insulin-like growth factor-I receptor; Kaempferol