Lycopene induces apoptosis by inhibiting nuclear translocation of β-catenin in gastric cancer cells

J Physiol Pharmacol. 2019 Aug;70(4). doi: 10.26402/jpp.2019.4.11. Epub 2019 Nov 15.

Abstract

Reactive oxygen species (ROS) promote the development and progression of cancer by their effects on several signaling pathways. Lycopene, a major carotenoid natural product, is known to display antioxidant activity and to induce apoptosis of cancer cells. The aim of the present study was to investigate the mechanism by which lycopene induces apoptosis of the human gastric cancer AGS cells. In the present study, we showed that lycopene reduces the viability of AGS cells by inducing DNA fragmentation and increasing the Bax/Bcl-2 ratio. To determine the mechanistic basis for these effects, studies were conducted to assess the effects of this carotenoid on activation and nuclear translocation of β-catenin, and the expression of β-catenin target genes in AGS cells. The results showed that lycopene reduces the levels of ROS. It also inhibits activation of β-catenin signaling by changing the Wnt/β-catenin multi-protein complex such as a reduction in phosphorylation of glycogen synthase kinase 3β [GSK3β] and an increase in adenomatous polyposis coli [APC] and β-transducin repeats-containing proteins [β-TrCP]). It suppresses nuclear translocation of β-catenin and the expression of the β-catenin target survival genes c-myc and cyclin D1. Lycopene induces apoptosis by reducing ROS levels and suppressing β-catenin-c-myc/cyclin D1 axis. Thus, lycopene induces apoptosis of gastric cancer cells by disrupting nuclear translocation of β-catenin and expression of key cell survival genes.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • DNA Fragmentation
  • Humans
  • Lycopene / pharmacology*
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / metabolism*
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • CCND1 protein, human
  • CTNNB1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Reactive Oxygen Species
  • beta Catenin
  • Cyclin D1
  • Lycopene