Physalis philadelphica
Lam, commonly known as a tomatillo, is a staple of the Mesoamerican cuisine. In our laboratory, an
ethyl acetate-soluble extract and four
withanolides [
ixocarpalactone A (IxoA), ixocarpalactone B, philadelphicalactone B, and withaphysacarpin] were isolated. Studies conducted on Hepa-1c1c7
hepatoma cells revealed that
withanolides were potent inducers of
quinone reductase, suggesting possible
cancer chemoprotective activity. Here we evaluated the antiproliferative properties of the
withanolides in SW480 human
colon cancer cells. IxoA, which is present in the edible part of the tomatillo, was selected for further evaluation. SW480 cells treated with IxoA showed cell cycle arrest in the G2/M phase, up-regulation of hyper-phosphorylated
retinoblastoma, and down-regulation of E2F-1 and DP-1. On the basis of flow cytometry analysis,
ethidium bromide/
acridine orange, and
4',6-diamidino-2-phenylindole staining, it was found that IxoA induces apoptosis in SW480 cells. Moreover, increased concentrations of the
pro-apoptotic protein, BIM/BOD, were found by western blot analysis and immunocytochemistry. Morphological examination revealed vacuole formation in cells treated with IxoA, and
Oil Red O staining showed that the vacuole content was nonlipid. Furthermore, immunocytochemistry demonstrated increased concentrations of
mucin 3 in IxoA-treated SW480 cells. These findings suggest that chemicals present in tomatillos (e.g. IxoA) may have
cancer chemopreventive properties.