Document Detail

Ixocarpalactone A isolated from the Mexican tomatillo shows potent antiproliferative and apoptotic activity in colon cancer cells.
MedLine Citation:
PMID:  17212786     Owner:  NLM     Status:  MEDLINE    
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.
Juliana K Choi; Genoveva Murillo; Bao-Ning Su; John M Pezzuto; A D Kinghorn; Rajendra G Mehta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The FEBS journal     Volume:  273     ISSN:  1742-464X     ISO Abbreviation:  FEBS J.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2007-01-10     Completed Date:  2007-02-02     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  5714-23     Citation Subset:  IM    
Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, IL, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Cycle / drug effects
Cell Line, Tumor
Colonic Neoplasms / drug therapy*,  metabolism
Down-Regulation / drug effects
Drug Screening Assays, Antitumor
E2F1 Transcription Factor / metabolism
Ergosterol / analogs & derivatives*,  chemistry,  therapeutic use
Physalis / chemistry*
Retinoblastoma Protein / metabolism
Transcription Factor DP1 / metabolism
Up-Regulation / drug effects
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/Retinoblastoma Protein; 0/TFDP1 protein, human; 0/Transcription Factor DP1; 0/ixocarpalactone A; 57-87-4/Ergosterol

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