β-Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK pathway

Arch Toxicol. 2013 Oct;87(10):1797-808. doi: 10.1007/s00204-013-1041-5. Epub 2013 Mar 28.

Abstract

β-Ionone is an end ring analog of β-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of β-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. We found that the β-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). β-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells. These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins. These results demonstrate potent ability of β-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / biosynthesis
  • DNA / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Norisoprenoids / administration & dosage
  • Norisoprenoids / pharmacology*
  • Resting Phase, Cell Cycle / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology

Substances

  • Norisoprenoids
  • DNA
  • beta-ionone
  • Extracellular Signal-Regulated MAP Kinases