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

The effects of sulforaphane (a natural product commonly found in broccoli) was investigated on hypoxia inducible factor-1 alpha (HIF-1 alpha) expression in HCT116 human colon cancer cells and AGS human gastric cancer cells. We found that hypoxia-induced HIF-1 alpha protein expression in HCT116 and AGS cells, while treatment with sulforaphane markedly and concentration-dependently inhibited HIF-1 alpha 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-1 alpha stability. However, degradation of HIF-1 alpha by sulforaphane was not mediated through the 26S proteasome pathway. We also found that the inhibition of HIF-1 alpha by sulforaphane was not mediated through AKT and extracellular signal-regulated kinase phosphorylation under hypoxic conditions. Finally, hypoxiainduced 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-1 alpha 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.