Ixocarpalactone A isolated from the Mexican tomatillo shows potent antiproliferative and apoptotic activity in colon cancer cells

Abstract

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.

Development of tomatillo (Physalis ixocarpa Brot.) autotetraploids and their chromosome and phenotypic characterization

“…It is a source of vitamins A and C, and it has been suggested that chemicals present in tomatillos, e.g. ixocarpalactone A, may have cancer chemopreventive properties (Choi et al 2006).…”

Withanolides and Related Steroids

“…Ixocarpolactones A (360) and B (361), isolated from P. philadelphica, exhibited significant inhibition of murine epidermal JB6 cell transformation (104) and ixocarpolactone A (360) present in the edible fruit of the plant showed potent antiproliferative and apoptotic activity in SW480 human colon cancer cells (247). Evaluation of 12 withaphysalins from P. minima and P. divaricata, including 331-334, showed only moderate cytotoxicity against the HCT-116 and H460 human cancer cell lines (154,186).…”

“…Accordingly, these bioactivity results should be considered with caution. Among the Physalis withanolides with an unmodified skeleton, potent cytotoxic activity has been reported for withangulatins A (511), B (94), and I (102), physangulin B (512), phyperunolide A (101), withaphysacarpin (195), philadelphicalactones A (197) and B (198), 18-hydroxywithanolide D (128), and withanone (513) (50,55,56,58,104,247).…”

Physalis development according to the growing season in the semi-arid region of the Bahia state, Brazil

“…In addition, pectins with a high potential for use in the food industry (Morales-Contreras et al 2018) can be extracted from the fruit. Besides, the extract from leaves, stem, fruits and calyx has an important pharmacological potential, due to its high antibacterial (Khan et al 2016) and chemopreventive activity (Choi et al 2006).…”