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.
Highlights
Cell division and programmed cell death constitute fundamental processes in the maintenance of tissue homeostasis
The results presented here suggest that neurymenolide A acts by destabilizing the mitotic spindle at the prometaphase transition in U-2 OS human osteosarcoma cells, which results in mitotic catastrophe leading to necrosis and apoptosis
Neurymenolide A Has Mild to Moderate Impact on the Growth of Cancerous Human Cell Lines
Summary
Cell division and programmed cell death constitute fundamental processes in the maintenance of tissue homeostasis. Dysfunctions in these mechanisms can lead to genetic instability, including. Mar. Drugs 2019, 17, 93 numerical and structural chromosomal aberrations; the latter represents one of the first recognized attributes of cancer cells [1]. Mitotic catastrophe can arise from a variety of cellular damages and failures at cell-cycle checkpoints, in particular the spindle assembly checkpoint. This latter is used by cells to control the stable kinetochore-microtubule attachments of chromosomes during mitosis [3]
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