Effect of mycalolides isolated from a marine sponge Mycale aff. nullarosette on actin in living cells

Yoko Hayashi-Takanaka, Yuto Kina, Fumiaki Nakamura, Shota Yamazaki, Masahiko Harata, Rob W.M.van Soest, Hiroshi Kimura, Youichi Nakao

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Abstract

Discovery of novel bioactive compounds is important not only for therapeutic purposes but also for understanding the mechanisms of biological processes. To screen bioactive compounds that affect nuclear morphology in marine organism extracts, we employed a microscopy-based assay using DNA staining of human cancer cells. A crude extract from a marine sponge Mycale aff. nullarosette, collected from the east coast of Japan, induced cellular binucleation. Fractionation of the extract led to the isolation of mycalolides A and B, and 38-hydroxymycalolide B as the active components. Mycalolides have been identified as marine toxins that induce depolymerization of the actin filament. Live cell imaging revealed that low concentrations of mycalolide A produce binucleated cells by inhibiting the completion of cytokinesis. At higher concentrations, however, mycalolide A causes immediate disruption of actin filaments and changes in cell morphology, yielding rounded cells. These results suggest that the completion of cytokinesis is a process requiring high actin polymerization activity. Furthermore, luciferase reporter assays with mycalolide A treatments support the view that the level of globular actin can affect transcription of a serum response gene.

Original languageEnglish
Article number7540
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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    Hayashi-Takanaka, Y., Kina, Y., Nakamura, F., Yamazaki, S., Harata, M., Soest, R. W. M. V., Kimura, H., & Nakao, Y. (2019). Effect of mycalolides isolated from a marine sponge Mycale aff. nullarosette on actin in living cells. Scientific reports, 9(1), [7540]. https://doi.org/10.1038/s41598-019-44036-2