Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death

Molecules

AbrahamJ. Vaisberg¹  NicoleS. Stivers²  GeraldB. Hammond³  JoséC. Aponte³  Ashraful Islam⁴  LavonaK. Casson⁴  ElsaM. Reyes-Reyes⁴  PaulaJ. Bates⁴ 

[1] Departamento de Ciencias Celulares y Moleculares y Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15102, Peru;Department of Biology, University of Louisville, Louisville, KY 40208, USA;Department of Chemistry, University of Louisville, Louisville, KY 40292, USA;Department of Medicine, University of Louisville, Louisville, KY 40202, USA;

关键词: plagiochiline A;    Plagiochila disticha;    cytokinesis;    abscission;   

DOI  :  10.3390/molecules23061418

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown