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

Author:

Yao Chih-Jung12,Lai Gi-Ming123,Yeh Chi-Tai2456,Lai Ming-Tang7,Shih Ping-Hsiao2,Chao Wan-Ju3,Whang-Peng Jacqueline12,Chuang Shuang-En3,Lai Tung-Yuan89

Affiliation:

1. Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan

2. Center of Excellence for Cancer Research, Taipei Medical University, Taipei 11031, Taiwan

3. National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan

4. Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei 23561, Taiwan

5. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 11031, Taiwan

6. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan

7. Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan

8. Department of Traditional Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan

9. Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 11031, Taiwan

Abstract

Honokiol, an active compound ofMagnolia 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 asABCG2,ABCC5,EpCAM,OCT-4,CD133,CD44, andβ-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 asβ-catenin and TCF-4 were decreased in honokiol-treated SP cells, while theβ-catenin degradation promoting kinase GSK-3α/βwas increased. Consistently, the protein levels ofβ-catenin downstream targets such asc-MycandCyclin D1were also downregulated. Furthermore, theβ-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.

Funder

Taipei Medical University

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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