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

Kathy K W AU YEUNG, Pui Ching Law, Joshua KO*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

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 down-regulated expression of the HCC tumor marker α-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-κB)/ DNA-binding activity. Concomitantly, expression of the phosphorylated form of the extracellular signal-regulated protein kinase (ERK) was prominently increased. Nevertheless, pre-treatment 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-κB signaling pathway.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalInternational Journal of Molecular Medicine
Volume23
Issue number2
DOIs
Publication statusPublished - 2009

Scopus Subject Areas

  • Genetics

User-Defined Keywords

  • Apoptosis
  • Astragalus saponin
  • Extracellular signal-regulated protein kinase
  • HepG2 cells
  • Nuclear factor-κB

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