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(S)-戈尼辛诱导 NCI-H460 细胞的 DNA 损伤、凋亡和 BIRC5 信使 RNA 水平降低。

(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells.

机构信息

1Departamento de Biologia Geral, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.

出版信息

Hum Exp Toxicol. 2014 Jan;33(1):3-13. doi: 10.1177/0960327113491506. Epub 2013 Jun 7.

Abstract

(R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.

摘要

(R)-戈尼辛(R-GNT)是从戈尼氏南星属植物中分离得到的一种次生代谢产物。由于其对肿瘤细胞的选择性细胞毒性和诱导细胞凋亡的能力,该分子引起了研究人员的关注。(S)-戈尼辛(S-GNT)是 R-GNT 的合成对映异构体,其作用机制在很大程度上尚不清楚。在这项研究中,我们研究了 S-GNT 在人非小细胞肺癌 NCI-H460 细胞中的活性。我们观察到,暴露于该化合物的细胞表现出浓度依赖性的细胞毒性。基于原位诱导细胞凋亡和彗星试验评估获得的数据,我们认为这种细胞毒性是由于该分子具有潜在的诱导 DNA 损伤的能力,从而通过细胞凋亡诱导细胞死亡。我们发现编码生存素蛋白的杆状病毒凋亡抑制剂重复包含 5 基因(BIRC5)的信使 RNA 水平显著降低。这一新发现可能解释了该化合物抑制肿瘤细胞增殖和诱导细胞凋亡的作用机制。

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