Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells

Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.

Abstract

Quercetin is one of the natural components from natural plant and it induces cell apoptosis in many human cancer cell lines. However, no available reports show that quercetin induces apoptosis and altered associated gene expressions in human gastric cancer cells, thus, we investigated the effect of quercetin on the apoptotic cell death and associated gene expression in human gastric cancer AGS cells. Results indicated that quercetin induced cell morphological changes and reduced total viability via apoptotic cell death in AGS cells. Furthermore, results from flow cytometric assay indicated that quercetin increased reactive oxygen species (ROS) production, decreased the levels of mitochondrial membrane potential (ΔΨm ), and increased the apoptotic cell number in AGS cells. Results from western blotting showed that quercetin decreased anti-apoptotic protein of Mcl-1, Bcl-2, and Bcl-x but increased pro-apoptotic protein of Bad, Bax, and Bid. Furthermore, quercetin increased the gene expressions of TNFRSF10D (Tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain), TP53INP1 (tumor protein p53 inducible nuclear protein 1), and JUNB (jun B proto-oncogene) but decreased the gene expression of VEGFB (vascular endothelial growth factor B), CDK10 (cyclin-dependent kinase 10), and KDELC2 (KDEL [Lys-Asp-Glu-Leu] containing 2) that are associated with apoptosis pathways. Thus, those findings may offer more information regarding the molecular, gene expression, and signaling pathway for quercetin induced apoptotic cell death in human gastric cancer cells.

Keywords: apoptosis; cDNA; gene expression; human gastric cancer cells; quercetin.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / genetics
  • Microarray Analysis
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quercetin / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • BCL2 protein, human
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Quercetin