Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells
Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells
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DOI：
10.3892/ijo.2015.3200
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发表时间：
2015-12-01
影响因子：
5.2
通讯作者：
Kim, Nam Deuk
中科院分区：
文献类型：
--
作者：
Kim, Dong Hwan;Sung, Bokyung;Kim, Nam Deuk
研究了萝卜硫素对HCT116人结肠癌细胞和AGS人胃癌细胞缺氧诱导因子-1 α (HIF-1 α)表达的影响。我们发现缺氧诱导HIF-1 α蛋白在HCT116和AGS细胞中的表达，而萝卜硫素处理显著且浓度依赖性地抑制了HIF-1 α在两种细胞系中的表达。萝卜硫素抑制缺氧诱导的血管内皮生长因子（VEGF）在HCT116细胞中的表达。萝卜硫素可调节缺氧对HIF-1 α稳定性的影响。然而，萝卜硫素对HIF-1 α的降解不是通过26S蛋白酶体途径介导的。我们还发现，在缺氧条件下，萝卜硫素对HIF-1 α的抑制不是通过AKT和细胞外信号调节的激酶磷酸化介导的。最后，萝卜硫素抑制缺氧诱导的HCT116细胞迁移。这些数据表明，萝卜硫素可能通过抑制HIF-1 α和VEGF的表达来抑制人类结肠癌的进展和癌细胞血管生成。综上所述，这些结果表明萝卜硫素是一种新的有效的化学预防药物，可用于治疗人类结肠癌患者。
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.