Astragalus saponins induce apoptosis via an ERK-independent NF-kappaB signaling pathway in the human hepatocellular HepG2 cell line

Int J Mol Med. 2009 Feb;23(2):189-96.


Astragalus membranaceus has been used to ameliorate the side effects of anti-neoplastic drugs. We recently reported that total Astragalus saponins (AST) possess anti-tumor properties in human colon cancer cells and tumor xenografts. Nevertheless, the precise mechanism of action has not been fully elucidated. The present study aimed to unveil the anti-carcinogenic potential of AST in HepG2 human hepatocellular carcinoma (HCC) cells and to clarify the signaling pathway. We demonstrated here that AST downregulated expression of the HCC tumor marker alpha-fetoprotein and suppressed HepG2 cell growth by inducing apoptosis. AST also caused caspase activation, poly(ADP-ribose) polymerase (PARP) cleavage, nuclear chromatin condensation, with downregulation of the anti-apoptotic proteins bcl-2 and bcl-xL and decreased nuclear factor-kappa B (NF-kappaB)/DNA-binding activity. Concomitantly, expression of the phosphorylated form of the extracellular signal-regulated protein kinase (ERK) was prominently increased. Nevertheless, pretreatment of ERK inhibitor PD98059 did not attenuate AST-induced PARP cleavage. Taken together, these results exemplify that AST induced growth inhibition and promoted apoptosis in HepG2 cells through modulation of an ERK-independent NF-kappaB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Astragalus Plant / chemistry*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Liver Neoplasms / metabolism
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Saponins / toxicity*
  • Signal Transduction*
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / metabolism


  • NF-kappa B
  • Saponins
  • alpha-Fetoproteins
  • Nitric Oxide Synthase Type II
  • Extracellular Signal-Regulated MAP Kinases