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萝卜硫素通过调节细胞周期蛋白依赖性激酶-细胞周期蛋白轴以及CD44变体4、5和7的表达来降低前列腺癌细胞的体外生长和增殖。

Sulforaphane Reduces Prostate Cancer Cell Growth and Proliferation In Vitro by Modulating the Cdk-Cyclin Axis and Expression of the CD44 Variants 4, 5, and 7.

作者信息

Rutz Jochen, Thaler Sarah, Maxeiner Sebastian, Chun Felix K-H, Blaheta Roman A

机构信息

Department of Urology, Goethe-University, 60323 Frankfurt am Main, Germany.

出版信息

Int J Mol Sci. 2020 Nov 18;21(22):8724. doi: 10.3390/ijms21228724.

Abstract

Prostate cancer patients whose tumors develop resistance to conventional treatment often turn to natural, plant-derived products, one of which is sulforaphane (SFN). This study was designed to determine whether anti-tumor properties of SFN, identified in other tumor entities, are also evident in cultivated DU145 and PC3 prostate cancer cells. The cells were incubated with SFN (1-20 µM) and tumor cell growth and proliferative activity were evaluated. Having found a considerable anti-growth, anti-proliferative, and anti-clonogenic influence of SFN on both prostate cancer cell lines, further investigation into possible mechanisms of action were performed by evaluating the cell cycle phases and cell-cycle-regulating proteins. SFN induced a cell cycle arrest at the S- and G2/M-phase in both DU145 and PC3 cells. Elevation of histone H3 and H4 acetylation was also evident in both cell lines following SFN exposure. However, alterations occurring in the Cdk-cyclin axis, modification of the p19 and p27 proteins and changes in CD44v4, v5, and v7 expression because of SFN exposure differed in the two cell lines. SFN, therefore, does exert anti-tumor properties on these two prostate cancer cell lines by histone acetylation and altering the intracellular signaling cascade, but not through the same molecular mechanisms.

摘要

肿瘤对传统治疗产生耐药性的前列腺癌患者常常求助于天然的植物衍生产品,其中之一就是萝卜硫素(SFN)。本研究旨在确定在其他肿瘤实体中已得到确认的SFN的抗肿瘤特性在培养的DU145和PC3前列腺癌细胞中是否也很明显。将细胞与SFN(1 - 20 μM)一起孵育,并评估肿瘤细胞的生长和增殖活性。在发现SFN对两种前列腺癌细胞系均有显著的抗生长、抗增殖和抗克隆形成作用后,通过评估细胞周期阶段和细胞周期调节蛋白,对可能的作用机制进行了进一步研究。SFN在DU145和PC3细胞中均诱导细胞周期停滞于S期和G2/M期。在暴露于SFN后,两种细胞系中组蛋白H3和H4的乙酰化水平也均明显升高。然而,由于SFN暴露,两种细胞系中Cdk - 细胞周期蛋白轴发生的改变、p19和p27蛋白的修饰以及CD44v4、v5和v7表达的变化有所不同。因此,SFN确实通过组蛋白乙酰化和改变细胞内信号级联反应对这两种前列腺癌细胞系发挥抗肿瘤特性,但并非通过相同的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c9e/7699211/68ab9725602a/ijms-21-08724-g001.jpg

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