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姜黄素通过抑制 TPA 诱导的 MCF-7 人乳腺癌细胞中 PKCα 依赖性 MMP 表达来抑制侵袭。

Curcumin suppresses the TPA-induced invasion through inhibition of PKCα-dependent MMP-expression in MCF-7 human breast cancer cells.

机构信息

Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, South Korea.

出版信息

Phytomedicine. 2012 Sep 15;19(12):1085-92. doi: 10.1016/j.phymed.2012.07.002. Epub 2012 Aug 22.

Abstract

Curcumin (diferuloylmethane) is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. Although anti-carcinogenic, anti-oxidant, anti-inflammation, and anti-angiogenic properties have been reported, the effect of curcumin on breast cancer metastasis is unknown. Matrix metalloproteinase-9 (MMP-9) is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells. Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Also, curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB/AP-1 pathway in MCF-7 cells. Curcumin may have potential value in restricting breast cancer metastasis.

摘要

姜黄素(二芳基甲烷)是一种源自植物姜黄(姜黄)的多酚,通常用作香料。尽管已报道其具有抗癌、抗氧化、抗炎和抗血管生成特性,但姜黄素对乳腺癌转移的影响尚不清楚。基质金属蛋白酶-9(MMP-9)是癌细胞侵袭的主要成分。在这项研究中,我们研究了姜黄素对 12-O-十四烷酰佛波醇-13-乙酸酯(TPA)诱导的 MMP-9 表达和细胞侵袭的抑制作用及其在 MCF-7 细胞中涉及的分子机制。我们的结果表明,姜黄素通过抑制 NF-κB 和 AP-1 激活来抑制 TPA 诱导的 MMP-9 表达和细胞侵袭。此外,姜黄素强烈抑制 TPA 诱导的 p38 和 JNK 磷酸化,并抑制 TPA 诱导的 PKCα 从细胞质向膜的易位,但不影响 PKCδ 的易位。这些结果表明,姜黄素介导的 TPA 诱导的 MMP-9 表达和细胞侵袭的抑制涉及 MCF-7 细胞中 PKCα、MAPK 和 NF-κB/AP-1 途径的抑制。姜黄素可能在限制乳腺癌转移方面具有潜在价值。

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