Antimitotic activity of methoxyconidiol, a meroterpene isolated from an ascidian.

Methoxyconidiol is a meroterpene previously extracted from the ascidian Aplidium aff. densum [A. Simon-Levert, A. Arrault, N. Bontemps-Subielos, C. Canal, B. Banaigs. Meroterpenes from the ascidian Aplidium aff. densum, J. Nat. Prod. 68 (2005) 1412-1415]. In the present work we investigated its antimitotic effect on eukaryotic cells by using a bioassay based on the sea urchin early embryo. This bioassay has been successfully used to evaluate the efficacy of antiproliferative agents and to rapidly determine the affected cell cycle phase. We demonstrated that methoxyconidiol inhibits the cleavages of sea urchin Sphaerechinus granularis and Paracentrotus lividus fertilized eggs. This meroterpene disrupts M-phase progression and completely blocks cytokinesis without having any effect on DNA replication. The treatment severely disturbs the establishment of a mitotic spindle, most likely by affecting microtubule dynamics. Moreover, while the cell cycle regulatory kinase cyclin B/CDK1 is activated, cyclin B proteolysis is inhibited, impeding the output of M-phase. This characteristic cell cycle arrest induced by methoxyconidiol in sea urchin eggs emphasizes the interest for this drug as a putative antiproliferative agent for tumor cells.