2'-Hydroxyflavanone induces apoptosis through Egr-1 involving expression of Bax, p21, and NAG-1 in colon cancer cells

Mol Nutr Food Res. 2012 May;56(5):761-74. doi: 10.1002/mnfr.201100651.

Abstract

Scope: Natural flavanones exhibit cancer preventive and/or therapeutic effects. The objective of this study was to investigate the molecular mechanism underlying the action of the antitumor activity of hydroxyflavanone using the HCT116 colon cancer cell line.

Methods and results: We investigated the effect of hydroxyflavanones on antitumor activity. We found that 2'-hydroxyflavanone (2'-HF) potently inhibited the clonogenicity of HCT116 cells. 2'-HF triggered apoptosis in both wild-type and p53-null HCT116 cells, as revealed by DNA fragmentation and caspase activation. 2'-HF upregulated nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression through induction of Egr-1. Silencing of NAG-1 or Egr-1 using small interfering RNA (siRNA) could attenuate 2'-HF-induced apoptosis. Egr-1 also upregulated the proapoptotic gene Bax and the cell cycle inhibitor p21.

Conclusion: Dietary 2'-HF may possess antitumor activity against human colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Binding Sites
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Dietary Supplements
  • Drug Screening Assays, Antitumor
  • Early Growth Response Protein 1 / metabolism
  • Flavanones / pharmacology*
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism
  • HCT116 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Promoter Regions, Genetic / drug effects
  • Receptors, Cell Surface / metabolism*
  • Survivin
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • 2'-hydroxyflavanone
  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • BIRC5 protein, human
  • Early Growth Response Protein 1
  • Flavanones
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Inhibitor of Apoptosis Proteins
  • Receptors, Cell Surface
  • Survivin
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • rho GTP-Binding Proteins