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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 170261, 14 pages
http://dx.doi.org/10.1155/2013/170261
Research Article

Cyclohexylmethyl Flavonoids Suppress Propagation of Breast Cancer Stem Cells via Downregulation of NANOG

1Stem Cell Program, Genomics Research Center, Academia Sinica, Nangang, Taipei 115, Taiwan
2Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 402, Taiwan
3Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan
4Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 804, Taiwan
5Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 112, Taiwan
6Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 300, Taiwan
7The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 402, Taiwan
8Graduate Institute of Clinical Medicine, Taipei Medical University, Sinyi District, Taipei 110, Taiwan

Received 7 February 2013; Accepted 2 March 2013

Academic Editor: Hui-Fen Liao

Copyright © 2013 Wen-Ying Liao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Breast cancer stem cells (CSCs) are highly tumorigenic and possess the capacity to self-renew. Recent studies indicated that pluripotent gene NANOG involves in regulating self-renewal of breast CSCs, and expression of NANOG is correlated with aggressiveness of poorly differentiated breast cancer. We initially confirmed that breast cancer MCF-7 cells expressed NANOG, and overexpression of NANOG enhanced the tumorigenicity of MCF-7 cells and promoted the self-renewal expansion of CD2 CD44+ CSC subpopulation. In contrast, knockdown of NANOG significantly affected the growth of breast CSCs. Utilizing flow cytometry, we identified five cyclohexylmethyl flavonoids that can inhibit propagation of NANOG-positive cells in both breast cancer MCF-7 and MDA-MB231 cells. Among these flavonoids, ugonins J and K were found to be able to induce apoptosis in non-CSC populations and to reduce self-renewal growth of CD2 CD44+ CSC population. Treatment with ugonin J significantly reduced the tumorigenicity of MCF-7 cells and efficiently suppressed formation of mammospheres. This suppression was possibly due to p53 activation and NANOG reduction as either addition of p53 inhibitor or overexpression of NANOG can counteract the suppressive effect of ugonin J. We therefore conclude that cyclohexylmethyl flavonoids can possibly be utilized to suppress the propagation of breast CSCs via reduction of NANOG.