Tailor-Made Fluorescent Trilobolide To Study Its Biological Relevance
Tailor-Made Fluorescent Trilobolide To Study Its Biological Relevance
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DOI：
10.1021/jm500690j
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发表时间：
2014-10-09
影响因子：
7.3
通讯作者：
Ruml, Tomas
中科院分区：
文献类型：
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作者：
Jurasek, Michal;Rimpelova, Silvie;Ruml, Tomas
三叶草素（Tb）是毒胡萝卜素的有效天然对应物，其在癌症临床试验中显示出有希望的结果。在这里，我们报告了一个合理的方法来研究这种倍半萜内酯的细胞内定位和生物活性。我们将Tb与通过不同长度的替代接头连接的发射绿色的Bodipy染料缀合。制备的生物缀合物的活细胞成像带来了明确的证据，即Tb-Bodipy定位于各种癌细胞系的内质网（ER）中。将定位信号与ER特异性染料进行比较。还研究了Tb缀合物的细胞毒性以及对线粒体生理学和一氧化氮释放的影响。大鼠腹膜细胞中的一氧化氮产生和细胞因子分泌表明这些内酯生物缀合物的免疫生物学潜力。总之，我们的Tb-Bodipy缀合物可以帮助我们揭示三叶草的分子机制，以进一步在生物医学应用中的潜在用途。
Trilobolide (Tb) is a potent natural counterpart of thapsigargin, which has shown promising results in cancer clinical trials. Here, we report a rational approach to study intracellular localization and biological activity of this sesquiterpene lactone. We conjugated Tb with a green emitting Bodipy dye attached by alternative linkers of different lengths. The live cell imaging of the prepared bioconjugates brought clear evidence that Tb-Bodipy localized in the endoplasmic reticulum (ER) of various cancer cell lines. The localization signal was compared with ER-specific dyes. Cytotoxicity of Tb conjugates and impact on the mitochondrial physiology and nitric oxide release were also studied. The nitric oxide production and cytokine secretion in rat peritoneal cells indicate immunobiological potential of these lactone bioconjugates. In summary, our Tb-Bodipy conjugates could help us to reveal the molecular mechanism of trilobolide for its further potential use in biomedical applications.