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

Kim,Dong  Hwan; Sung,Bokyung; Kang,Yong  Jung; Hwang,Seong  Yeon; Kim,Min  Jeong; Yoon,Jeong-Hyun; Im,Eunok; Kim,Nam  Deuk

doi:10.3892/ijo.2015.3200

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

Authors:
- Dong Hwan Kim
- Bokyung Sung
- Yong Jung Kang
- Seong Yeon Hwang
- Min Jeong Kim
- Jeong-Hyun Yoon
- Eunok Im
- Nam Deuk Kim
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Affiliations: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea
Published online on: October 13, 2015 https://doi.org/10.3892/ijo.2015.3200
Pages: 2226-2232

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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.

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