Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2013 Aug 2;8(8):e71889. doi: 10.1371/journal.pone.0071889. Print 2013.
Laulimalide is a microtubule-binding drug that was originally isolated from marine sponges. High concentrations of laulimalide stabilize microtubules and inhibit cell division similarly to paclitaxel; however, there are important differences with respect to the nature of the specific cellular defects between these two drugs and their binding sites on the microtubule. In this study, we used Caenorhabditis elegans embryos to investigate the acute effects of laulimalide on microtubules in vivo, with a direct comparison to paclitaxel. We observed surprising dose-dependent effects for laulimalide, whereby microtubules were stabilized at concentrations above 100 nM, but destabilized at concentrations between 50 and 100 nM. Despite this behaviour at low concentrations, laulimalide acted synergistically with paclitaxel to stabilize microtubules when both drugs were used at sub-effective concentrations, consistent with observations of synergistic interactions between these two drugs in other systems. Our results indicate that laulimalide induces a concentration-dependent, biphasic change in microtubule polymer dynamics in the C. elegans embryo.
拉罗肽是一种微管结合药物，最初从海洋海绵中分离出来。高浓度的拉罗肽稳定微管并抑制细胞分裂，类似于紫杉醇；然而，这两种药物在特定细胞缺陷的性质及其在微管上的结合位点方面存在重要差异。在这项研究中，我们使用秀丽隐杆线虫胚胎在体内研究拉罗肽对微管的急性作用，并与紫杉醇进行直接比较。我们观察到拉罗肽的剂量依赖性作用令人惊讶，即微管在高于 100 nM 的浓度下稳定，但在 50 至 100 nM 的浓度下不稳定。尽管在低浓度下有这种行为，但当两种药物在亚有效浓度下使用时，拉罗肽与紫杉醇协同作用稳定微管，这与在其他系统中观察到这两种药物协同相互作用的结果一致。我们的结果表明，拉罗肽在秀丽隐杆线虫胚胎中诱导微管聚合物动力学的浓度依赖性双相变化。
