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

机译:青霉素通过抑制NF-κB的活化来抑制MMP-9基因的表达从而抑制乳腺癌细胞的迁移和侵袭。

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摘要

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.
机译:基质金属蛋白酶9(MMP-9)在各种类型的癌细胞的侵袭和转移中起着核心作用。在这里,我们证明了从植物延胡索(Corydalis turtschaninovii tuber(Papaveraceae))分离得到的生物碱-青霉素可以抑制人类乳腺癌细胞的迁移和侵袭。我们进一步显示,青光氨酸以剂量依赖的方式显着阻断佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)诱导的MMP-9表达和活性。报道基因和电泳迁移率迁移分析的结果表明,青霉素可通过抑制核转录因子核因子-κB(NF-κB)的激活来抑制MMP-9表达。此外,青霉素可减弱PMA诱导的IκBα降解和NF-κB的核易位。最后,我们还发现,在高转移性MDA-MB-231乳腺癌细胞系中,青霉素可抑制侵袭和MMP-9表达。综上所述,我们的发现表明,青霉素的MMP-9抑制活性及其减弱IκBα和NF-κB活性的能力可能在治疗上可用作控制乳腺癌生长和侵袭性的新手段。

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