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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 146136, 10 pages
http://dx.doi.org/10.1155/2013/146136
Research Article

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/β-Catenin Signaling and Apoptosis Induction

1Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
2Center of Excellence for Cancer Research, Taipei Medical University, Taipei 11031, Taiwan
3National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan
4Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei 23561, Taiwan
5Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 11031, Taiwan
6Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan
7Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
8Department of Traditional Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
9Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 11031, Taiwan

Received 18 December 2012; Accepted 12 March 2013

Academic Editor: Ching-Liang Hsieh

Copyright © 2013 Chih-Jung Yao 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

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT.