Active Component of Antrodia cinnamomea Mycelia Targeting Head and Neck Cancer Initiating Cells through Exaggerated Autophagic Cell Death

• Main Authors: Ching-Wen Chang, Chien-Chih Chen, Meng-Ju Wu, Yu-Syuan Chen, Chin-Chu Chen, Sen-Je Sheu, Ting-Wei Lin, Shiu-Huey Chou, Shu-Chun Lin, Chung-Ji Liu, Te-Chang Lee, Chih-Yang Huang, Jeng-Fan Lo
• Format: Article
• Language: English
• Published: Hindawi Limited 2013-01-01
• Series: Evidence-Based Complementary and Alternative Medicine
• Online Access: http://dx.doi.org/10.1155/2013/946451
• ISSN: 1741-427X; 1741-4288

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer. Previously, we identify head and neck cancer initiating cells (HN-CICs), which are highly tumorigenic and resistant to conventional therapy. Therefore, development of drug candidates that effectively target HN-CICs would benefit future head and neck cancer therapy. In this study, we first successfully screened for an active component, named YMGKI-1, from natural products of Antrodia cinnamomea Mycelia (ACM), which can target the stemness properties of HNSCC. Treatment of YMGKI-1 significantly downregulated the aldehyde dehydrogenase (ALDH) activity, one of the characteristics of CIC in HNSCC cells. Additionally, the tumorigenic properties of HNSCC cells were attenuated by YMGKI-1 treatment in vivo. Further, the stemness properties of HN-CICs, which are responsible for the malignancy of HNSCC, were also diminished by YMGKI-1 treatment. Strikingly, YMGKI-1 also effectively suppressed the cell viability of HN-CICs but not normal stem cells. Finally, YMGKI-1 induces the cell death of HN-CICs by dysregulating the exaggerated autophagic signaling pathways. Together, our results indicate that YMGKI-1 successfully lessens stemness properties and tumorigenicity of HN-CICs. These findings provide a new drug candidate from purified components of ACM as an alternative therapy for head and neck cancer in the future.