维生素K3作为一种通过线粒体相关凋亡途径发挥作用的抗乳腺癌抗癌剂的潜力。
The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway.
作者信息
Akiyoshi Takeshi, Matzno Sumio, Sakai Mika, Okamura Noboru, Matsuyama Kenji
机构信息
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
出版信息
Cancer Chemother Pharmacol. 2009 Dec;65(1):143-50. doi: 10.1007/s00280-009-1016-7. Epub 2009 May 16.
PURPOSE
We tried to clarify the cytotoxic mechanism of VK(3) using the breast cancer cell line MCF-7.
METHODS
Cytotoxicity was measured via intracellular esterase activity. DNA fragmentation was assessed by agarose gel electrophoresis. JC-1 staining was applied to measure mitochondrial dysfunction. Caspase activation and reactive oxidative species (ROS) generation were also measured.
RESULTS
VK(3) exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC(50) of 14.2 microM. JC-1 staining revealed that VK(3) caused mitochondrial dysfunction including a disappearance of mitochondrial membrane potential. Additional investigation showed that the mitochondrial damage was induced by the generation of ROS and the subsequent activation of caspase-7 and -9.
CONCLUSIONS
Our findings demonstrate that VK(3)-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.
目的
我们试图利用乳腺癌细胞系MCF-7阐明维生素K3（VK(3)）的细胞毒性机制。
方法
通过细胞内酯酶活性测定细胞毒性。采用琼脂糖凝胶电泳评估DNA片段化。运用JC-1染色来测定线粒体功能障碍。同时也检测了半胱天冬酶激活和活性氧（ROS）生成情况。
结果
VK(3)表现出细胞毒性，导致MCF-7细胞出现DNA片段化，半数抑制浓度（IC(50)）为14.2微摩尔。JC-1染色显示VK(3)引起线粒体功能障碍，包括线粒体膜电位消失。进一步研究表明，线粒体损伤是由ROS生成以及随后半胱天冬酶-7和-9的激活所诱导的。
结论
我们的研究结果表明，VK(3)诱导的细胞凋亡是由线粒体相关途径选择性启动的，可能对乳腺癌化疗有用。
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