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

Abstract EN

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.