Glaucine inhibits breast cancer cell migration and invasion by inhibiting MMP-9 gene expression through the suppression of NF-κB activation.

Glaucine inhibits breast cancer cell migration and invasion by inhibiting MMP-9 gene expression through the suppression of NF-κB activation.
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DOI:
10.1007/s11010-015-2339-9
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发表时间:
2015-05
影响因子:
4.3
通讯作者:
Shim, Sungbo
Shim, Sungbo
中科院分区:
生物学3区
文献类型:
--
作者:
Kang, Hyereen;Jang, Sung-Wuk;Pak, Jhang Ho;Shim, Sungbo

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基质金属蛋白酶-9(MMP-9)在多种类型的癌细胞的侵袭和转移中起着中心作用。在这里,我们证明,从植物Corpatienturtschaninovii块茎(罂粟科)中分离的生物碱,可以抑制人类乳腺癌细胞的迁移和侵袭。我们进一步表明,格劳辛显着阻断佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)诱导的MMP-9的表达和活性的剂量依赖性方式。报告基因和电泳迁移率变动分析的结果显示,蓝绿色通过抑制核转录因子核因子-κB(NF-κB)的活化来抑制MMP-9的表达。此外,Glaucine还能减弱PMA诱导的IκBα降解和NF-κB核转位。最后,我们还发现,在高转移性MDA-MB-231乳腺癌细胞系中,蓝绿色抑制侵袭和MMP-9的表达。综上所述,我们的研究结果表明,蓝绿色的MMP-9抑制活性及其减弱IκBα和NF-κB活性的能力可能是治疗上有用的,作为控制乳腺癌生长和侵袭的新手段。
Matrix metalloproteinase-9 (MMP-9) plays a central role in the invasion and metastasis of various types of cancer cells. Here, we demonstrate that glaucine, an alkaloid isolated from the plant Corydalis turtschaninovii tuber (Papaveraceae), can inhibit the migration and invasion of human breast cancer cells. We further show that glaucine significantly blocks phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression and activity in a dose-dependent manner. Results from reporter gene and electrophoretic mobility shift assays revealed that glaucine inhibits MMP-9 expression by suppressing activation of the nuclear transcription factor nuclear factor-κB (NF-κB). Moreover, glaucine attenuates PMA-induced IκBα degradation and nuclear translocation of NF-κB. Finally, we also found that glaucine inhibits invasion and MMP-9 expression in the highly metastatic MDA-MB-231 breast cancer cell line. Taken together, our findings indicate that the MMP-9 inhibitory activity of glaucine and its abilities to attenuate IκBα and NF-κB activities may be therapeutically useful as a novel means of controlling breast cancer growth and invasiveness.
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