Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells

Biomed Pharmacother. 2008 Nov;62(9):659-66. doi: 10.1016/j.biopha.2008.08.002. Epub 2008 Aug 31.

Abstract

Objective: We sought to determine whether paeoniflorin enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relationship between this apoptosis and NF-kappaB activation.

Methods: Paeoniflorin was diluted to different concentrations and added to gastric carcinoma cells (SGC-7901) at different times. Western blot was used to test the expression of NF-kappaB in nuclear and I kappaB alpha, p-I kappaB alpha, IKK alpha in cytoplasm. Further, the intranuclear expression of NF-kappaB was confirmed by ELISA assay. The impact of paeoniflorin and 5-fluorouracil on cell apoptosis of gastric carcinoma cells was estimated by flow cytometry.

Results: Paeoniflorin revealed dramatic inhibition of NF-kappaB activity in the nuclei of the cells. The inhibition pattern of NF-kappaB was exhibited in a time- and dose-dependent manner, which was confirmed by Western blot and ELISA. Decreased nuclear translocation of NF-kappaB induced by paeoniflorin was found by preventing I kappaB alpha phosphorylation. Moreover, 5-fluorouracil-induced cell apoptosis was promoted by paeoniflorin in gastric carcinoma cells.

Conclusions: Paeoniflorin can inhibit NF-kappaB activity of SGC-7901 cells, and enhance 5-fluorouracil-induced apoptosis of gastric carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Benzoates / pharmacology*
  • Bridged-Ring Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Fluorouracil / pharmacology*
  • Glucosides / pharmacology*
  • Humans
  • I-kappa B Proteins / metabolism*
  • Monoterpenes
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Phosphorylation
  • Stomach Neoplasms

Substances

  • Antineoplastic Agents
  • Benzoates
  • Bridged-Ring Compounds
  • Glucosides
  • I-kappa B Proteins
  • Monoterpenes
  • NF-kappa B
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • peoniflorin
  • Fluorouracil