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

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.

• Authors: Dong Hwan Kim, Bokyung Sung, Yong Jung Kang, Seong Yeon Hwang, Min Jeong Kim, Jeong-Hyun Yoon, Eunok Im, Nam Deuk Kim
• Journal: International journal of oncology (Int J Oncol) Vol. 47 Issue 6 Pg. 2226-32 (Dec 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 26498863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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