Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells

Int J Oncol. 2015 Dec;47(6):2226-32. doi: 10.3892/ijo.2015.3200. Epub 2015 Oct 13.

Abstract

The effects of sulforaphane (a natural product commonly found in broccoli) was investigated on hypoxia inducible factor-1α (HIF-1α) expression in HCT116 human colon cancer cells and AGS human gastric cancer cells. We found that hypoxia-induced HIF-1α protein expression in HCT116 and AGS cells, while treatment with sulforaphane markedly and concentration-dependently inhibited HIF-1α expression in both cell lines. Treatment with sulforaphane inhibited hypoxia-induced vascular endothelial growth factor (VEGF) expression in HCT116 cells. Treatment with sulforaphane modulated the effect of hypoxia on HIF-1α stability. However, degradation of HIF-1α by sulforaphane was not mediated through the 26S proteasome pathway. We also found that the inhibition of HIF-1α by sulforaphane was not mediated through AKT and extracellular signal-regulated kinase phosphorylation under hypoxic conditions. Finally, hypoxia-induced HCT116 cell migration was inhibited by sulforaphane. These data suggest that sulforaphane may inhibit human colon cancer progression and cancer cell angiogenesis by inhibiting HIF-1α and VEGF expression. Taken together, these results indicate that sulforaphane is a new and potent chemopreventive drug candidate for treating patients with human colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Blotting, Western
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cell Movement / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • HCT116 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Isothiocyanates / pharmacology*
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Anticarcinogenic Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isothiocyanates
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • sulforaphane