An echo-contrast agent, Levovist, lowers the ultrasound intensity required to induce apoptosis of human leukemia cells

An echo-contrast agent, Levovist, lowers the ultrasound intensity required to induce apoptosis of human leukemia cells
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DOI:
10.1016/j.canlet.2005.10.032
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发表时间:
2006-10-08
期刊:
影响因子:
9.7
通讯作者:
Misaki, Takuro
Misaki, Takuro
中科院分区:
医学1区
文献类型:
--
作者:
Ando, Hidetaka;Feril, Loreto B., Jr.;Misaki, Takuro

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为了验证超声造影剂(ECA)对超声诱导的细胞凋亡的影响,以先前显示的在有或没有Levovist(ECA)的情况下诱导最佳细胞凋亡的强度对白血病细胞系(Jurkat、Molt-4和U937)进行超声处理。结果表明,在所有三种细胞系中均可诱导活力丧失和凋亡,基于活力和DNA片段化测定,Molt-4的凋亡最高。这种发现得到了相应的增加的细胞与低线粒体膜电位,高超氧化物产生,增加的细胞内钙浓度,和磷酸化的组蛋白H2 AX超声处理后的支持。最佳超声条件为0.3 W/cm(2),1 MHz,10%占空因数,脉冲频率为100 Hz;但在利声显存在下,在0.2 W/cm(2)时观察到细胞杀伤诱导的明显偏移。虽然这些结果进一步证实了先前关于超声诱导的细胞凋亡的发现,但它们也表明,当需要低得多的强度时,使用增强因子(例如添加ECA)可能在癌症治疗中有用。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
To verify the effect of echo-contrast agent (ECA) on apoptosis induced by ultrasound, leukemia cell lines (Jurkat, Molt-4 and U937) were sonicated at intensities previously shown to induce optimal apoptosis with or without Levovist, an ECA. The results showed that loss of viability and apoptosis can be induced in all three cell lines, apoptosis highest with Molt-4, based on viability and DNA fragmentation assay. Such finding was supported by corresponding increase of cells with low mitochondrial membrane potential, high superoxide production, increased intracellular calcium concentration, and phosphorylation of histone H2AX after sonication. Optimal ultrasound condition was 0.3 W/cm(2), 1 MHz, 10% duty factor pulsed at 100 Hz; but in the presence of Levovist, an apparent shift of cell killing induction was observed at 0.2 W/cm(2). While these results further confirmed previous findings on ultrasound-induced apoptosis, they also suggest that use of an enhancing factor, such as addition of ECA, may be useful in cancer therapy when a much lower intensity is desired. (c) 2005 Elsevier Ireland Ltd. All rights reserved.