Piperlongumine inhibits NF-κB activity and attenuates aggressive growth characteristics of prostate cancer cells.

Piperlongumine inhibits NF-κB activity and attenuates aggressive growth characteristics of prostate cancer cells.
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DOI:
10.1002/pros.22739
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发表时间:
2014-02
期刊:
影响因子:
2.8
通讯作者:
Kolenko, Vladimir M.
Kolenko, Vladimir M.
中科院分区:
医学3区
文献类型:
--
作者:
Ginzburg, Serge;Golovine, Konstantin V.;Makhov, Petr B.;Uzzo, Robert G.;Kutikov, Alexander;Kolenko, Vladimir M.

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NF-κB活性升高先前已在前列腺癌细胞系中被证实为激素非依赖性或转移性特征的发展。我们观察了胡椒明(PL),一种存在于长胡椒植物中的生物活性生物碱/酰胺,对雄激素非依赖性前列腺癌细胞中NF-κB通路的影响。采用荧光素酶报告基因检测和p50和p65核易位的Western blot分析评估NF-κB活性。采用ELISA法检测IL-6、IL-8、MMP-9水平。我们还评估了前列腺癌细胞经PL处理后的细胞粘附性和侵袭性。随着PL浓度的增加,NF-κB dna结合活性直接下调,p50和p65亚基的核易位减少。IL-6、IL-8、MMP-9和ICAM-1的表达减弱,前列腺癌细胞对基质的粘附和侵袭性降低。pl介导的NF-κB活性抑制可降低前列腺癌细胞的侵袭性生长特征。
Elevated NF-κB activity has been previously demonstrated in prostate cancer cell lines as hormone-independent or metastatic characteristics develop. We look at the effects of piperlongumine (PL), a biologically active alkaloid/amide present in piper longum plant, on the NF-κB pathway in androgen-independent prostate cancer cells. NF-κB activity was evaluated using Luciferase reporter assays and Western blot analysis of p50 and p65 nuclear translocation. IL-6, IL-8, and MMP-9 levels were assessed using ELISA. Cellular adhesion and invasiveness properties of prostate cancer cells treated with PL were also assessed. NF-κB DNA-binding activity was directly down-regulated with increasing concentrations of PL, along with decreased nuclear translocation of p50 and p65 subunits. Expression of IL-6, IL-8, MMP-9, and ICAM-1 was attenuated, and a decrease of cell-to-matrix adhesion and invasiveness properties of prostate cancer cells were observed. PL-mediated inhibition of NF-κB activity decreases aggressive growth characteristics of prostate cancer cells in vitro.
雄激素受体的磷酸化与激素难治性前列腺癌患者的生存率降低有关。
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