Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/24197
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 16844/19259 (87%)
Visitors : 7165807      Online Users : 593
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/24197


    Title: Disruption of Porphyrin Homeostasis by Inhih/biting ABCG2 with Cyclohexylmethyl Flavonoids Suppresses Propagation oof Stetem-like Breast Cancer Cells
    Authors: Wen-Ying Liao (廖紋瑩)
    Chih-Chuang Liaw (廖志中)
    Chien-Shu Chen (陳建樹)
    Guey-Horng Wang (王貴弘)
    Yuan-Chao Huang
    Jimmy Susanto
    Sheng-Chu Kuo (郭盛助)
    Chia-Ning Shen (沈家寧)
    Date: 2011
    Issue Date: 2011-06-23 14:56:53 (UTC+8)
    Abstract: Breast cancer stem cells express ATP-binding cassette sub-family G member 2 (ABCG2) and display multidrug resistance. Recent studies have shown that suppression of ABCG2 affects self-renewal of embryonic stem cells and inhibits proliferation of breast cancer cells. We therefore hypothesized that ABCG2 is involved in the maintenance of breast cancer stem cells and that cytotoxic ABCG2 inhibitors can be utilized to eliminate drug-resistant breast cancer stem cells. We have found that the ABCG2+ subpopulation of MCF-7 cells is able to efflux protoporphyrin IX (PPIX), suggesting that the endogenous role of ABCG2 in breast cancer cells is to transport excess porphyrins. Utilizing a porphyrin-efflux assay, we have identified two cytotoxic cyclohexylmethyl flavonoids isolated from Helminthostachys zeylanica that can inhibit ABCG2 by binding to its nucleotide-binding domain. Treatment with ugonin J or K not only inhibited porphyrin efflux and the side-population phenotype, but induced apoptosis in both ABCG2+ and ABCG2- cell populations and suppressed expansion of ABCG2+CD24-/lowCD44+ stem-like breast cancer cells in mammosphere cultures. We also found that the suppressive effect of ugonin J on propagation of stem-like breast cancer cells was mediated by PPIX accumulation, which in turn led to activation of p53 and reduction of Nanog. Overexpression of Nanog counteracted the suppressive effect of ugonin J. In conclusion, the current work identifies two novel cyclohexylmethyl flavonoids that can act as cytotoxic ABCG2 inhibitors to induce apoptosis in breast cancer cells and suppress propagation of stem-like breast cancer cells via reduction of Nanog.
    Appears in Collections:[Pharmacy and Science] 2011 Taiwanese-Russian Organic, Medicinal and Bio Chemistry Interactions & PST Medicinal Chemistry Symposium
    [Dept. of Cosmetic Science and institute of cosmetic science] Proceedings

    Files in This Item:

    File Description SizeFormat
    op-09.pdf116KbAdobe PDF406View/Open


    All items in CNU IR are protected by copyright, with all rights reserved.


    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback