Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death

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

Physangulidines A, B, and C: Three New Antiproliferative Withanolides from <i>Physalis angulata</i> L.

Bioassay-directed fractionation of the whole plant of <i>Physalis angulata</i> L. afforded three new antiproliferative withanolides with an unusual carbon framework: physangulidines A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>). Structures of the three isomeric withanolides were determined by a combination of HRMS, NMR spectroscopic, and X-ray crystallographic methods. Each has shown significant antiproliferative activity against DU145 prostate cancer cells. Physangulidine A (<b>1</b>) was further tested against a wide range of additional cancer cell lines and found to exhibit significant antiproliferative activity

Physangulidines A, B, and C: Three New Antiproliferative Withanolides from <i>Physalis angulata</i> L.

Bioassay-directed fractionation of the whole plant of <i>Physalis angulata</i> L. afforded three new antiproliferative withanolides with an unusual carbon framework: physangulidines A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>). Structures of the three isomeric withanolides were determined by a combination of HRMS, NMR spectroscopic, and X-ray crystallographic methods. Each has shown significant antiproliferative activity against DU145 prostate cancer cells. Physangulidine A (<b>1</b>) was further tested against a wide range of additional cancer cell lines and found to exhibit significant antiproliferative activity