A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy

Tumour Biol. 2014 Dec;35(12):12021-30. doi: 10.1007/s13277-014-2501-0. Epub 2014 Aug 22.

Abstract

In the present study, we investigated the effects of 3-O-β-D-galactopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl-28-O-[α-L-arabinopyranosyl-(1 → 4)-α-L-arabinopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranosyl] quillaic acid, named compound 1, on the induction of apoptosis and autophagy in human gastric cancer AGS cells. Compound 1, a triterpenoid saponin isolated from the root of Adenophora triphylla var. japonica, effectively inhibited the growth of AGS cells by inducing apoptosis, as well as autophagy. Apoptosis by compound 1 treatment was associated with activation of caspases, release of cytochrome c, and increased ratio of Bax/Bcl-2. Autophagy by compound 1 treatment was indicated by LC3-II protein expression. We also found an increase in phosphorylation of p38 and JNK and a decrease in phosphorylation of ERK and Akt after compound 1 treatment. Furthermore, pretreatment with p38 inhibitor SB202190 completely inhibited compound 1-induced activation of caspases and cleavage of PARP1, whereas pretreatment with SB202190 synergistically increased the protein expression of LC3-II. These results suggest that compound 1 distinctly induces apoptotic and autophagic cell death and the increased autophagy by SB202190 protects compound 1-induced AGS cell death. Our findings provide an important clue for exploring the potential anticancer role of compound 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Autophagy / drug effects
  • Campanulaceae / chemistry*
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System
  • Microtubule-Associated Proteins / metabolism
  • NF-kappa B / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Stomach Neoplasms / metabolism*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • NF-kappa B
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Saponins
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspases