title: Ivermectin exhibits potent anti-mitotic activity.
abstract: Ivermectin (IVM) is a pharmaceutical used as an anti-parasitic drug in livestock, companion animals and humans. The primary site of action of IVM is believed to be glutamate-gated chloride channels (GluCls). However we have recently reported a direct interaction between IVM and nematode tubulin with micromolar affinity. Here we report that IVM also interacts with mammalian tubulin. To test this possibility, we used the tubulin polymerization assay and found that IVM increased the degree of polymerization of mammalian tubulin. Furthermore when HeLa cells were exposed to IVM it stabilized the mammalian tubulin against the depolymerizing effects of cold temperatures, and prevented the replication of the HeLa cells in vitro. However, the IVM-induced inhibition of HeLa cell division was reversible. The data suggests that mammalian microtubules bound IVM and were stabilized by IVM at micromolar concentrations. IVM may thus affect the dynamics of tubulin polymerization and depolymerization, which in turn can result in cell death. Given that IVM is already approved for use in humans, its development as an anti-mitotic is a potentially appealing option.
authors: Institute of Parasitology, McGill University-Macdonald Campus, Sainte-Anne-de-Bellevue, H9X 3V9 Quebec, Canada.
authors: Shoaib
authors: S
authors: Ashraf
authors: Institute of Parasitology, McGill University-Macdonald Campus, Sainte-Anne-de-Bellevue, H9X 3V9 Quebec, Canada. Electronic address: roger.prichard@mcgill.ca.
authors: Roger
authors: R
authors: Prichard
mesh_terms: D050256:Antimitotic Agents / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology*; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D058105:Polymerization / Q000187:drug effects; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects*
chemical_list: D050256:Antimitotic Agents; D000977:Antiparasitic Agents; D014404:Tubulin; D007559:Ivermectin
keywords: Anti-mitotic; Ivermectin; Mammalian tubulin