Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death
AffiliationUniv Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Med
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CitationStivers, 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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AbstractWe 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 G(2)/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.
NoteOpen access journal.
VersionFinal published version
SponsorsU.S. Department of Defense Prostate Cancer Research Program (PCRP) of the Office of the Congressionally Directed Medical Research Medical Research Program (CDMRP) [W81XWH-07-1-0299]
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