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-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.
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Dong Hwan
DH
Kim
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Bokyung
B
Sung
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Yong Jung
YJ
Kang
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Seong Yeon
SY
Hwang
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Min Jeong
MJ
Kim
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Jeong-Hyun
JH
Yoon
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Eunok
E
Im
Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea.
Nam Deuk
ND
Kim
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D045325:HCT116 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D017879:Isothiocyanates / Q000494:pharmacology*; D013454:Sulfoxides; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D016588:Anticarcinogenic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017879:Isothiocyanates; D013454:Sulfoxides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C016766:sulforaphane