8-O-acetylharpagide, an active compound isolated from A. taiwanensis selectively induced G2/M phase arrest and radiosensitivity in hypopharyngeal cancer cells

  • Biochem Biophys Rep. 2026 Jan 6:45:102431. doi: 10.1016/j.bbrep.2025.102431.
Wan-Yu Yang  1 ,  Yung-Cheng Wang  2  3 ,  Yun-Lian Lin  4  5 ,  Kuei-Yuan Hou  2 ,  Wan-Chun Li  6  7  8  9 ,  Yi-Jang Lee  1  10
Affiliations
  • 1. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming Chiao Tung University, Taipei, 112, Taiwan.
  • 2. Department of Radiology, Cathay General Hospital, Taipei, 106, Taiwan.
  • 3. School of Medicine, Fu Jen Catholic University, Taipei, 242, Taiwan.
  • 4. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 40402, Taiwan.
  • 5. Department of Pharmacy, National Taiwan University, Taipei, 10050, Taiwan.
  • 6. Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 7. Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 8. Oral Medicine Innovation Center (OMIC), National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 9. Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 10. Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei Branch, Taipei, 112, Taiwan.
PMID: 41550497 DOI: 10.1016/j.bbrep.2025.102431
Abstract

Hypopharyngeal Cancer (HPC) is a rare but most malignant subtype of head and neck squamous cell carcinoma (HNSCC). Conventional chemo-radiotherapy is the primary approach for the treatment of HPC, while the efficacy is limited and complications. Previously, we have isolated an active compound (AT-1) identified as 8-O-acetylharpagide from Ajuga taiwanensis. Because Ajuga extracts are both edible and known for their anti-cancer properties, it is worthwhile to investigate whether AT-1 can inhibit cancers of otolaryngological origin. In this study, we compared the cell killing effects of AT-1 on FaDu HPC cells and periodontal ligament (PDL) cells. The results showed that AT-1 was more toxic on FaDu cells (IC50 = 0.88 mM) than on PDL cells (IC50 = 1.65 mM), yielding a selectivity index (SI) ≈ 1.85. AT-1 caused significant G2/M phase arrest in FaDu cells with a dose-dependent manner. Concomitantly, high concentration of AT-1 could induce necrosis-like fraction and late Apoptosis in FaDu cells. Notably, AT-1 did not influence the cell cycle redistribution and cell death in PDL cells under the same condition of treatment. Furthermore, AT-1 enhanced the radiosensitivity of FaDu cells rather than PDL cells, suggesting that AT-1 induced G2/M phase arrest remains sensitive to ionizing radiation known as a principle of radiobiology. Taken together, current data indicate that AT-1 raises selectively efficacy on HPC cells by increasing G2/M phase arrest, Apoptosis, as well as radiosensitivity.

Keywords
8-O-Acetylharpagide; AT-1; Apoptosis; G2/M phase arrest; Hypopharyngeal cancer; Radiosensitivity.
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