Laulimalide induces dose-dependent modulation of microtubule behaviour in the C. elegans embryo.
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.
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Megha
M
Bajaj
Martin
M
Srayko
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D018942:Macrolides / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D018942:Macrolides; C117305:laulimalide; D017239:Paclitaxel