tailieunhanh - Báo cáo khoa học: Ixocarpalactone A isolated from the Mexican tomatillo shows potent antiproliferative and apoptotic activity in colon cancer cells

Physalis philadelphicaLam, 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), ixocarpalac-tone B, philadelphicalactone B, and withaphysacarpin] were isolated. Stud-ies conducted on Hepa-1c1c7 hepatoma cells revealed that withanolides were potent inducers of quinone reductase, suggesting possible cancer chemo-protective activity. | ễFEBS Journal Ixocarpalactone A isolated from the Mexican tomatillo shows potent antiproliferative and apoptotic activity in colon cancer cells Juliana K. Choi1 Genoveva Murillo2 Bao-Ning Su3 John M. Pezzuto4 A. D. Kinghorn3 and Rajendra G. Mehta2 1 Department of SurgicalOncology College of Medicine University of Illinois at Chicago IL USA 2 Carcinogenesis and Chemoprevention Division Life Sciences Group IIT Research Institute Chicago IL USA 3 MedicinalChemistry and Pharmacognosy College of Pharmacy Ohio State University Columbus OH USA 4 Department of MedicinalChemistry and Molecular Pharmacology Schoolof Pharmacy and PharmaceuticalSciences Purdue University West Lafayatte IN USA Keywords apoptosis colon cancer ixocarpalactone A Physalis philadelphica tomatillo Correspondence R. G. Mehta Carcinogenesis and Chemoprevention Division IIT Research Institute 10 West 35th Street Chicago IL 60616 USA Fax 1 312 567 4931 Tel 1 312 567 4970 E-mail RMehta@ Received 20 September 2006 accepted 27 October 2006 doi 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 ixocarpalac-tone 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 chemo-protective 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 bro-mide acridine orange and 4 6-diamidino-2-phenylindole staining it was found .

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