Physangulidine A, a Withanolide from <i>Physalis angulata</i>, Perturbs the Cell Cycle and Induces Cell Death by Apoptosis in Prostate Cancer Cells

Recently, our group reported the discovery of three new withanolides, physangulidines A–C, from <i>Physalis angulata</i>. In this study, the biological effects of physangulidine A (<b>1</b>), which was the most active and abundant of the three new constituents, are described. It was found that <b>1</b> significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines. Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that <b>1</b> induces cell cycle arrest in the G₂/M phase and causes defective mitosis. It was determined also that <b>1</b> produces programed cell death by apoptosis, as evidenced by biochemical markers and distinct changes in cell morphology. These results imply that the antimitotic and proapoptotic effects of <b>1</b> may contribute significantly to the biological activities and potential medicinal properties of its plant of origin