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萘基查耳酮诱导白血病细胞系凋亡和半胱天冬酶激活:线粒体损伤、氧化应激与细胞死亡的关系。

Naphthylchalcones induce apoptosis and caspase activation in a leukemia cell line: The relationship between mitochondrial damage, oxidative stress, and cell death.

机构信息

Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.

出版信息

Bioorg Med Chem. 2010 Nov 15;18(22):8026-34. doi: 10.1016/j.bmc.2010.09.025. Epub 2010 Sep 16.

Abstract

In this study, we investigated the effects of 24 chalcone derivatives from 2-naphthylacetophenone toward a lymphoblastic leukemia cell line (L1210). Three compounds, called R7, R13, and R15, presented concentration- and time-dependent cytotoxicity and induced cellular death by apoptosis via mitochondrial injury and oxidative stress. The effects of these compounds appear to occur through different mechanisms because R13 and R7 induced a greater disturbance of mitochondrial potential, and all compounds induced disturbances of cellular ATP content and increased caspase-3 activity before cellular death. These compounds also interfered with antioxidant enzymes activities and GSH content through different mechanisms.

摘要

在这项研究中,我们研究了 24 种来自 2-萘基苯乙酮的查尔酮衍生物对淋巴母细胞白血病细胞系(L1210)的影响。三种化合物,称为 R7、R13 和 R15,表现出浓度和时间依赖性细胞毒性,并通过线粒体损伤和氧化应激诱导细胞凋亡导致细胞死亡。这些化合物的作用机制似乎不同,因为 R13 和 R7 引起更大的线粒体电位紊乱,并且所有化合物在细胞死亡之前都会引起细胞内 ATP 含量的紊乱和 caspase-3 活性的增加。这些化合物还通过不同的机制干扰抗氧化酶活性和 GSH 含量。

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