Targeting cancer initiating cells by promoting cell differentiation and restoring chemosensitivity via dual inactivation of STAT3 and Src activity using an active component of Antrodia cinnamomea mycelia
Metrics: PDF 1652 views | HTML 2779 views | ?
Ching-Wen Chang1,*, Yu-Syuan Chen1,*, Chien-Chih Chen2,*, Ik-On Chan1, Chin-Chu Chen3, Sen-Je Sheu3, Ting-wei Lin3, Shiu-Huey Chou4, Chung-Ji Liu5, Te-Chang Lee6, Jeng-Fan Lo1,7,8,9
1Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
2Department of Biotechnology, Hungkuang University, Taichung, Taiwan
3Grape King Inc., Taoyuan County, Taiwan
4Department of Life Science, Fu-Jen University, Taipei, Taiwan
5Department of Oral and Maxillofacial Surgery, Mackay Memorial Hospital, Taipei, Taiwan
6Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
7Graduate Institute of Chinese Medical Science and Institute of Medical Science, China Medical University, Taichung, Taiwan
8Genome Research Center, National Yang-Ming University, Taipei, Taiwan
9Department of Dentistry, Taipei Veterans General Hospital, Taipei, Taiwan
*These authors contributed equally to this work
Jeng-Fan Lo, email: [email protected]
Keywords: ergone, cancer initiating cells, STAT3, Src, differentiation
Received: April 08, 2016 Accepted: September 14, 2016 Published: September 22, 2016
Cancer initiating cells (CICs) represent a subpopulation of cancer cells, which are responsible for tumor growth and resistance to chemotherapy. Herein, we first used a cell-based aldehyde dehydrogenase (ALDH) activity assay to identify that YMGKI-2 (also named as Ergone), an active component purified from Antrodia cinnamomea Mycelia extract (ACME), effectively abrogated the ALDH activity and abolished the CICs in head and neck squamous cell carcinoma cells (HNSCCs). Consequently, YMGKI-2 treatment suppressed self-renewal ability and expression of stemness signature genes (Oct-4 and Nanog) of sphere cells with enriched CICs. Moreover, YMGKI-2 treated sphere cells displayed reduction of CICs properties and promotion of cell differentiation, but not significant cytotoxicity. YMGKI-2 treatment also attenuated the tumorigenicity of HNSCC cells in vivo. Mechanistically, treatment of YMGKI-2 resulted in inactivation of STAT3 and Src. Lastly, combinatorial treatments with YMGKI-2 and standard chemotherapeutic drugs (cisplatin or Fluorouracil) restored the chemosensivity on sphere cells and cisplatin-resistant HNSCC cells. Together, we demonstrate that YMGKI-2 treatment effectively induces differentiation and reduces tumorigenicity of CICs. Further, combined treatment of YMGKI-2 and conventional chemotherapy can overcome chemoresistance. These results suggest that YMGKI-2 treatment may be used to improve future clinical responses in head and neck cancer treatment through targeting CICs.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.