Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1127, Fortaleza, Ceará, Brazil.
Chem Biol Interact. 2010 Feb 12;183(3):369-79. doi: 10.1016/j.cbi.2009.11.030. Epub 2009 Dec 4.
(+)-Cordiaquinone J is a 1,4-naphthoquinone isolated from the roots of Cordia leucocephala that has antifungal and larvicidal effects. However, the cytotoxic effects of (+)-cordiaquinone J have never being explored. In the present study, the effect of (+)-cordiaquinone J on tumor cells viability was investigated, showing IC(50) values in the range of 2.7-6.6muM in HL-60 and SF-295 cells, respectively. Studies performed in HL-60 leukemia cells indicated that (+)-cordiaquinone J (1.5 and 3.0muM) reduces cell viability and 5-bromo-2-deoxyuridine incorporation after 24h of incubation. (+)-Cordiaquinone J showed rapid induction of apoptosis, as indicated by phosphatidylserine externalization, caspase activation, DNA fragmentation, morphologic changes, and rapid induction of necrosis, as indicated by the loss of membrane integrity and morphologic changes. (+)-Cordiaquinone J altered the redox potential of cells by inducing the depletion of reduced GSH intracellular content, the generation of reactive oxygen species and the loss of mitochondrial membrane potential. However, pre-treatment of cells with N-acetyl-l-cysteine abolished most of the observed effects related to (+)-cordiaquinone J treatment, including those involving apoptosis and necrosis induction.
（+）-cordiaquinone J 是从 Cordia leucocephala 的根部分离得到的一种 1,4-萘醌，具有抗真菌和杀幼虫作用。然而，（+）-cordiaquinone J 的细胞毒性作用从未被探索过。在本研究中，研究了（+）-cordiaquinone J 对肿瘤细胞活力的影响，结果表明在 HL-60 和 SF-295 细胞中分别具有 2.7-6.6μM 的 IC50 值。在 HL-60 白血病细胞中的研究表明，（+）-cordiaquinone J（1.5 和 3.0μM）在孵育 24 小时后降低细胞活力和 5-溴-2-脱氧尿苷的掺入。（+）-cordiaquinone J 表现出快速诱导细胞凋亡，如磷脂酰丝氨酸外翻、半胱天冬酶激活、DNA 片段化、形态变化以及快速诱导坏死，如膜完整性丧失和形态变化。（+）-cordiaquinone J 通过诱导还原型 GSH 细胞内含量的耗竭、活性氧的产生和线粒体膜电位的丧失来改变细胞的氧化还原电位。然而，用 N-乙酰-l-半胱氨酸预处理细胞可消除与（+）-cordiaquinone J 处理相关的大多数观察到的作用，包括诱导凋亡和坏死的作用。
