Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death.

Autor: Stivers NS; Department of Biology, University of Louisville, Louisville, KY 40208, USA. nsstiv01@gmail.com.; Department of Medicine, University of Louisville, Louisville, KY 40202, USA. nsstiv01@gmail.com., Islam A; Department of Medicine, University of Louisville, Louisville, KY 40202, USA. ashrafulislam01@gmail.com.; Department of Clinical Biochemistry, University of Tabuk, Tabuk 71491, Saudi Arabia. ashrafulislam01@gmail.com., Reyes-Reyes EM; Department of Medicine, University of Louisville, Louisville, KY 40202, USA. emreye01@email.arizona.edu.; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA. emreye01@email.arizona.edu., Casson LK; Department of Medicine, University of Louisville, Louisville, KY 40202, USA. lavona.casson@louisville.edu., Aponte JC; Department of Chemistry, University of Louisville, Louisville, KY 40292, USA. jose.c.aponte@nasa.gov., Vaisberg AJ; Departamento de Ciencias Celulares y Moleculares y Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15102, Peru. abraham.vaisberg@upch.pe., Hammond GB; Department of Chemistry, University of Louisville, Louisville, KY 40292, USA. gb.hammond@louisville.edu., Bates PJ; Department of Medicine, University of Louisville, Louisville, KY 40202, USA. paula.bates@louisville.edu.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2018 Jun 12; Vol. 23 (6). Date of Electronic Publication: 2018 Jun 12.
DOI: 10.3390/molecules23061418
Abstrakt: 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.
Databáze: MEDLINE
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