Synergistic cytotoxic effect of the microtubule inhibitor marchantin A from Marchantia polymorpha and the Aurora kinase inhibitor MLN8237 on breast cancer cells in vitro

Planta medica
J Sophie JensenElin Soffia Olafsdottir

Abstract

Macrocyclic bisbibenzyls are a class of characteristic compounds, exclusively produced by liverworts. They are attracting increasing attention due to their wide range of biological activities, including antibacterial, antifungal, and antioxidative properties as well as cytotoxicity. Marchantin A is a cyclic bisbibenzyl that has previously been isolated from Marchantia polymorpha and other liverwort species and has been shown to exert cytotoxic effects. In the present study we found that the Icelandic M. polymorpha species produces marchantin A and through an in vitro cell growth inhibition assay, marchantin A was shown to induce a reduction in cell viability of breast cancer cell lines A256 (IC₅₀ = 5.5 µM), MCF7 (IC₅₀ = 11.5 µM), and T47D (IC₅₀ = 15.3 µM). The effect was considerably increased in all cell lines in a synergistic manner when the Aurora-A kinase inhibitor MLN8237 was added simultaneously. Fluorescence microscopy confirmed the antimicrotubular effect of marchantin A, and cell cycle analysis indicated enhanced cell division failure when combining this mitotic-spindle inhibitor with the checkpoint modulator.

Citations

Jul 31, 2012·Nature Genetics·Michael KrauthammerRuth Halaban
Mar 17, 2016·ACS Chemical Neuroscience·Nathaniel S Woodling, Katrin I Andreasson
Sep 7, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Sophie JensenElin Soffia Olafsdottir
Jun 30, 2019·Breast Cancer Research and Treatment·Vladislav KorobeynikovElena Shagisultanova
Jan 1, 2015·The Journal of Pathology. Clinical Research·Margret AradottirSigridur K Bodvarsdottir
Feb 22, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mari KogisoXiao-Nan Li
Oct 12, 2017·Journal of Natural Products·Yoshinori Asakawa, Agnieszka Ludwiczuk

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