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Inhibitory effects of 4-hydroperoxy-2-decenoic acid ethyl ester on phorbol ester- and TGF-β1-induced MMPs expression.
Free Radical Research ( IF 3.6 ) Pub Date : 2019-10-14 , DOI: 10.1080/10715762.2019.1675874
Tetsuro Kamiya 1 , Miho Tanaka 1 , Hirokazu Hara 1 , Eiji Yamaguchi 2 , Akichika Itoh 2 , Tetsuo Adachi 1
Affiliation  

Matrix metalloproteinases (MMPs), zinc-containing proteinases, play a critical role in tumour progression by degrading extracellular matrix components. MMP2 and MMP9 are secreted from tumour-associated macrophages as well as tumour cells and have been implicated in the formation of the tumour microenvironment. Therefore, the inhibition of these MMPs may suppress tumour progression and metastasis. 4-Hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE) is known to cause apoptosis in the human lung cancer cell line A549 by inducing endoplasmic reticulum (ER) stress. However, the effects of HPO-DAEE on tumour progression remain unclear. HPO-DAEE pre-treatment significantly suppressed phorbol 12-myristate 13-acetate (TPA)-triggered MMP activation in human monocytic THP-1 cells. It also enhanced the expression of haem oxygenase-1, an antioxidant enzyme, and suppressed the TPA-triggered intracellular accumulation of reactive oxygen species (ROS). Furthermore, HPO-DAEE suppressed transforming growth factor-β1-triggered human prostate cancer PC3 cell migration and this was accompanied by the inhibition of MMP expression and activities. The present results indicate that HPO-DAEE may exert inhibitory effects on tumour progression by suppressing MMP expression and activities.

中文翻译:

4-氢过氧-2-癸烯酸乙酯对佛波酯和TGF-β1诱导的MMPs表达的抑制作用。

基质金属蛋白酶(MMPs)是一种含锌的蛋白酶,通过降解细胞外基质成分而在肿瘤进展中起关键作用。MMP2和MMP9从与肿瘤相关的巨噬细胞以及肿瘤细胞中分泌,并且与肿瘤微环境的形成有关。因此,抑制这些MMPs可能会抑制肿瘤的进展和转移。已知4-羟基氧-2-癸烯酸乙酯(HPO-DAEE)通过诱导内质网(ER)应激而导致人肺癌细胞系A549凋亡。但是,HPO-DAEE对肿瘤进展的影响尚不清楚。HPO-DAEE预处理可显着抑制人单核细胞THP-1细胞中佛波醇12-肉豆蔻酸酯13-乙酸酯(TPA)触发的MMP活化。它还增强了血红素加氧酶-1(一种抗氧化酶)的表达,并抑制了TPA触发的细胞内活性氧(ROS)的积累。此外,HPO-DAEE抑制了转化生长因子-β1触发的人类前列腺癌PC3细胞迁移,并伴有MMP表达和活性的抑制。目前的结果表明,HPO-DAEE可能通过抑制MMP表达和活性而对肿瘤进展产生抑制作用。
更新日期:2019-11-01
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