VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells
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VI-14,一种新型黄酮衍生物,抑制人乳腺癌细胞的迁移和侵袭

DOI:
10.1016/j.taap.2012.04.011
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发表时间:
2012-06-01
影响因子:
3.8
通讯作者:
Guo, Qinglong
Guo, Qinglong
中科院分区:
医学3区
文献类型:
--
作者:
Li, Fanni;Li, Chenglin;Guo, Qinglong

文献摘要

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黄酮类化合物具有显著的抗肿瘤活性,包括抗血管生成、抗肿瘤转移和促细胞凋亡。在此,我们报告,第一次,VI-14,一种新的类黄酮衍生物,具有抗癌特性。本研究的目的是研究VI-14在乳腺癌细胞中的抗迁移和抗侵袭活性。我们的数据表明VI-14抑制MDA-MB-231和MDA-MB-435人乳腺癌细胞的粘附、迁移和侵袭。用VI-14处理的MDA-MB-231细胞在蛋白质和mRNA水平上显示ECM降解相关蛋白包括基质金属蛋白酶2(MMP-2)和9(MMP-9)的活性和表达降低。同时,VI-14处理诱导MDA-MB-231细胞中金属蛋白酶组织抑制剂1(TIMP-1)和2(TIMP-2)的上调表达。Western blotting结果显示,在VI-14处理的MDA-MB-231细胞中,MAPK信号通路的关键组分,包括ERK、JNK和P38的磷酸化水平显著降低。此外,VI-14处理显著降低核水平和核因子-κ B(NF-κ B)和激活蛋白-1(AP-1)的结合能力。总之,我们的数据表明,VI-14治疗抑制乳腺癌细胞的迁移和运动,VI-14可能是一种潜在的癌症治疗化合物。(C)2012 Elsevier Inc. All rights reserved.
It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Westem blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. (C) 2012 Elsevier Inc. All rights reserved.