Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling
Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling
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DOI：
10.1021/acs.jafc.6b02195
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发表时间：
2016-07-13
影响因子：
6.1
通讯作者：
Lee, Hong Jin
中科院分区：
文献类型：
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作者：
Bao, Cheng;Kim, Min Chae;Lee, Hong Jin
尽管异硫氰酸酯对乳腺肿瘤发生的抑制作用已得到广泛研究，但人们对萝卜硫素对乳腺癌侵袭性的影响知之甚少。在这里，磺胺萘显着抑制三阴性SUM 159人乳腺癌细胞的迁移和侵袭，并抑制基质金属蛋白酶2和9（MMP-2和MMP-9）的表达和活性。Hedgehog（Hh）通路作为一种上游信号调节剂，被磺胺草芬显著抑制。特别是，睫状体定位的Gli 1和其核转位被阻断，以时间依赖性的方式由磺胺草芬。结论：Vismodegib和Gli 1基因敲低下调Hh信号通路可降低细胞的迁移和侵袭能力以及MMP-2和MMP-9的表达。这些结果表明，通过抑制Hh/Gli 1信号转导，可降低MMP-2和MMP-9的活性和人乳腺癌细胞的细胞侵袭力，表明对乳腺癌的侵袭和转移的潜在疗效，磺胺草芬。
Although inhibition of mammary tumorigenesis by isothiocyanates has been widely studied, little is known about the effects of sulforaphene on invasiveness of breast cancer. Here, sulforaphene significantly inhibited the migration and invasion of triple-negative SUM159 human breast cancer cells and suppressed the expression and activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog (Hh) pathway, as an upstream signaling modulator, was significantly suppressed by sulforaphene. In particular, ciliary localization of Gli1 and its nuclear translocation were blocked by sulforaphene in a time dependent manner. Consistently, downregulation of Hh signaling by vismodegib and Gli1 knockdown reduced the cellular migration and invasion as well as the expression of MMP-2 and MMP-9. These results indicate that the suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells, suggesting the potential efficacy of sulforaphene against breast cancer invasion and metastasis.