Next Article in Journal
Jellyfish-Associated Microbiome in the Marine Environment: Exploring Its Biotechnological Potential
Previous Article in Journal
New Source of 3D Chitin Scaffolds: The Red Sea Demosponge Pseudoceratina arabica (Pseudoceratinidae, Verongiida)
Previous Article in Special Issue
Synergistic AML Cell Death Induction by Marine Cytotoxin (+)-1(R), 6(S), 1’(R), 6’(S), 11(R), 17(S)-Fistularin-3 and Bcl-2 Inhibitor Venetoclax
Article Menu

Export Article

Open AccessArticle
Mar. Drugs 2019, 17(2), 93; https://doi.org/10.3390/md17020093

Neurymenolide A, a Novel Mitotic Spindle Poison from the New Caledonian Rhodophyta Phacelocarpus neurymenioides

1
UMR ENTROPIE (IRD—Université de La Réunion—CNRS), Laboratoire d’Excellence Labex-CORAIL, Institut de Recherche pour le Développement (IRD), BP A5, 98848 Nouméa CEDEX, New Caledonia, France
2
Sorbonne Université, CNRS, USR 3151, Protein Phosphorylation & Human Diseases, Station Biologique de Roscoff, CS 90074, 29688 Roscoff CEDEX, France
3
UMR 7272 CNRS, Marine Natural Products Team, Nice Institute of Chemistry (ICN), University Nice Sophia Antipolis, Parc Valrose, 02 F-06108 Nice CEDEX, France
4
Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, 29688 Roscoff CEDEX, France
5
Department of Biological Sciences, Columbia University, New York, NY 10027, USA
*
Authors to whom correspondence should be addressed.
Received: 17 December 2018 / Revised: 21 January 2019 / Accepted: 23 January 2019 / Published: 1 February 2019
Full-Text   |   PDF [7443 KB, uploaded 1 February 2019]   |  

Abstract

The marine α-pyrone macrolide neurymenolide A was previously isolated from the Fijian red macroalga, Neurymenia fraxinifolia, and characterized as an antibacterial agent against antibiotic-resistant strains that also exhibited moderate cytotoxicity in vitro against cancer cell lines. This compound was also shown to exhibit allelopathic effects on Scleractinian corals. However, to date no mechanism of action has been described in the literature. The present study showed, for the first time, the isolation of neurymenolide A from the New Caledonian Rhodophyta, Phacelocarpus neurymenioides. We confirmed the compound’s moderate cytotoxicity in vitro against several human cell lines, including solid and hematological malignancies. Furthermore, we combined fluorescence microscopy and flow cytometry to demonstrate that treatment of U-2 OS osteosarcoma human cells with neurymenolide A could block cell division in prometaphase by inhibiting the correct formation of the mitotic spindle, which induced a mitotic catastrophe that led to necrosis and apoptosis. Absolute configuration of the stereogenic center C-17 of neurymenolide A was deduced by comparison of the experimental and theoretical circular dichroism spectra. Since the total synthesis of this compound has already been described, our findings open new avenues in cancer treatment for this class of marine molecules, including a new source for the natural product. View Full-Text
Keywords: New Caledonia; Phacelocarpus neurymenioides; Rhodophyta; neurymenolide A; mitotic spindle poison; mitotic catastrophe; necrosis; apoptosis New Caledonia; Phacelocarpus neurymenioides; Rhodophyta; neurymenolide A; mitotic spindle poison; mitotic catastrophe; necrosis; apoptosis
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Motuhi, S.-E.; Feizbakhsh, O.; Foll-Josselin, B.; Baratte, B.; Delehouzé, C.; Cousseau, A.; Fant, X.; Bulinski, J.C.; Payri, C.E.; Ruchaud, S.; Mehiri, M.; Bach, S. Neurymenolide A, a Novel Mitotic Spindle Poison from the New Caledonian Rhodophyta Phacelocarpus neurymenioides. Mar. Drugs 2019, 17, 93.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top