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Molecules 2018, 23(6), 1418; https://doi.org/10.3390/molecules23061418

Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death

1
Department of Biology, University of Louisville, Louisville, KY 40208, USA
2
Department of Medicine, University of Louisville, Louisville, KY 40202, USA
3
Department of Clinical Biochemistry, University of Tabuk, Tabuk 71491, Saudi Arabia
4
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA
5
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA
6
Departamento de Ciencias Celulares y Moleculares y Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
*
Author to whom correspondence should be addressed.
Received: 30 May 2018 / Accepted: 8 June 2018 / Published: 12 June 2018
(This article belongs to the Section Natural Products Chemistry)
Full-Text   |   PDF [970 KB, uploaded 12 June 2018]   |  

Abstract

We previously reported on the isolation and biological activities of plagiochiline A (1), a 2,3-secoaromadendrane-type sesquiterpenoid from the Peruvian medicinal plant, Plagiochila disticha. This compound was found to have antiproliferative effects on a variety of solid tumor cell lines, as well as several leukemia cell lines. Other researchers have also noted the cytotoxicity of plagiochiline A (isolated from different plant species), but there are no prior reports regarding the mechanism for this bioactivity. Here, we have evaluated the effects of plagiochiline A on cell cycle progression in DU145 prostate cancer cells. A cell cycle analysis indicated that plagiochiline A caused a significant increase in the percentage of cells in the G2/M phase when compared with control cells. When cells were stained and observed by fluorescence microscopy to examine progress through the mitotic phase, we found a significant increase in the proportion of cells with features of late cytokinesis (cells connected by intercellular bridges) in the plagiochiline A-treated samples. These results suggest that plagiochiline A inhibits cell division by preventing completion of cytokinesis, particularly at the final abscission stage. We also determined that plagiochiline A reduces DU145 cell survival in clonogenic assays and that it induces substantial cell death in these cells. View Full-Text
Keywords: plagiochiline A; Plagiochila disticha; cytokinesis; abscission plagiochiline A; Plagiochila disticha; cytokinesis; abscission
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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).

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Stivers, N.S.; Islam, A.; Reyes-Reyes, E.M.; Casson, L.K.; Aponte, J.C.; Vaisberg, A.J.; Hammond, G.B.; Bates, P.J. Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death. Molecules 2018, 23, 1418.

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