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组蛋白去乙酰化酶抑制剂可诱导幕上原始神经外胚层肿瘤细胞死亡。

Histone deacetylase inhibitors induce cell death in supratentorial primitive neuroectodermal tumor cells.

作者信息

Kumar K Saravana, Sonnemann Jürgen, Beck James F

机构信息

Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.

出版信息

Oncol Rep. 2006 Nov;16(5):1047-52.

Abstract

Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic agents with the capacity to induce differentiation and/or apoptosis of cancer cells. The objective of this study was to evaluate the activity of HDIs against supratentorial primitive neuroectodermal tumor (sPNET) cells. We show that the HDIs, suberoylanilide hydroxamic acid, sodium butyrate, and trichostatin A, induced cell death, and activated caspase-3 and -9 in a sPNET cell line, PFSK. The poly-caspase inhibitor z-VAD-fmk partially prevented the action of HDIs, as judged by determining the mitochondrial membrane potential and by quantifying internucleosomal DNA fragmentation. In conclusion, the HDIs explored possess potent activity against sPNET cells, suggesting that HDIs may be effective in the treatment of sPNET.

摘要

组蛋白去乙酰化酶抑制剂(HDIs)是一类有前景的新型抗肿瘤药物,具有诱导癌细胞分化和/或凋亡的能力。本研究的目的是评估HDIs对幕上原始神经外胚层肿瘤(sPNET)细胞的活性。我们发现,HDIs,即辛二酰苯胺异羟肟酸、丁酸钠和曲古抑菌素A,在sPNET细胞系PFSK中诱导细胞死亡,并激活半胱天冬酶-3和-9。通过测定线粒体膜电位和定量核小体间DNA片段化判断,多半胱天冬酶抑制剂z-VAD-fmk部分阻止了HDIs的作用。总之,所研究的HDIs对sPNET细胞具有强大的活性,提示HDIs可能对sPNET的治疗有效。

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