title: Active Component of Antrodia cinnamomea Mycelia Targeting Head and Neck Cancer Initiating Cells through Exaggerated Autophagic Cell Death.
abstract: 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.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, No. 155, Section 2, Li-Nong Street, Taipei 11221, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Chang
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chen
authors.forename: Meng-Ju
authors.initials: MJ
authors.lastname: Wu
authors.forename: Yu-Syuan
authors.initials: YS
authors.lastname: Chen
authors.forename: Chin-Chu
authors.initials: CC
authors.lastname: Chen
authors.forename: Sen-Je
authors.initials: SJ
authors.lastname: Sheu
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Lin
authors.forename: Shiu-Huey
authors.initials: SH
authors.lastname: Chou
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Lin
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Jeng-Fan
authors.initials: JF
authors.lastname: Lo