title: Synergistic cytotoxic effect of the microtubule inhibitor marchantin A from Marchantia polymorpha and the Aurora kinase inhibitor MLN8237 on breast cancer cells in vitro.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: J Sophie
authors.initials: JS
authors.lastname: Jensen
authors.forename: Sesselja
authors.initials: S
authors.lastname: Omarsdottir
authors.forename: Jenny B
authors.initials: JB
authors.lastname: Thorsteinsdottir
authors.forename: Helga M
authors.initials: HM
authors.lastname: Ogmundsdottir
authors.forename: Elin S
authors.initials: ES
authors.lastname: Olafsdottir
mesh_terms: D064127:Aurora Kinases; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004357:Drug Synergism; D004988:Ethers, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047008:Marchantia / Q000737:chemistry*; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D001381:Azepines; D001632:Bibenzyls; D004273:DNA, Neoplasm; D004988:Ethers, Cyclic; C550258:MLN 8237; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D050257:Tubulin Modulators; C096123:marchantin A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases