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

Sep 22, 2026

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Hypopharyngeal cancer (HPC) is a rare, highly malignant head and neck squamous cell carcinoma subtype with limited benefit from conventional chemo-radiotherapy and significant complications. An active compound (AT-1), identified as 8-O-acetylharpagide from Ajuga taiwanensis, was evaluated for selective effects on FaDu HPC cells versus periodontal ligament (PDL) cells. AT-1 showed stronger toxicity in FaDu cells, induced dose-dependent G2/M arrest, and promoted necrosis-like fraction and late apoptosis at high concentrations, while PDL cells were comparatively unaffected. AT-1 also enhanced radiosensitivity in FaDu cells, supporting selective efficacy via G2/M arrest, apoptosis, and radiosensitization.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

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Introduction

Hypopharyngeal cancer overview

Ajuga taiwanensis and bioactive compounds

Study rationale

Biochemistry and Biophysics Reports 45 (2026) 102431 Contents lists available at ScienceDirect Biochemistry and Biophysics Reports journal [homepage:](homepage: www.elsevier.com/locate/bbrep)[ www.elsevier.com/locate/bbrep](homepage: www.elsevier.com/locate/bbrep) | 8-O-acetylharpagide, an active compound isolated from A. taiwanensis selectively induced G2/M phase arrest and radiosensitivity in hypopharyngeal cancer cells
Wan-Yu Yanga,1, Yung-Cheng Wang b,c,1, Yun-Lian Lind,e, Kuei-Yuan Hou b, Wan-Chun Lif,g,h,i, Yi-Jang Lee a,j,*
a Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming Chiao Tung University, Taipei, 112, Taiwan b Department of Radiology, Cathay General Hospital, Taipei, 106, Taiwan
c School of Medicine, Fu Jen Catholic University, Taipei, 242, Taiwan
d Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 40402, Taiwan e Department of Pharmacy, National Taiwan University, Taipei, 10050, Taiwan
f Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan g Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan h Oral Medicine Innovation Center (OMIC), National Yang Ming Chiao Tung University, Taipei, Taiwan i Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan
j Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei Branch, Taipei, 112, Taiwan | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords: Hypopharyngeal cancer AT-1
8-O-Acetylharpagide G2/M phase arrest Apoptosis Radiosensitivity | | 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 dosedependent 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 asa 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. | 1. Introduction Hypopharyngeal cancer (HPC) is a rare and aggressive malignancy arising from the hypopharynx, the lower portion of the pharynx that connects the oropharynx to the esophagus. HPC accounts for 2–14 % of whole head and neck squamous cell carcinoma (HNSCC), while it is typically diagnosed at advanced stages with approximately 70 % of cases suffered from lymphatic invasion and poor prognosis after chemoradiotherapy [1–3]. Squamous cell carcinoma (SCC) constitutes over 95 % of HPC based on the histological subtype, and mainly locates the pyriform sinuses [4]. The management of HPC involves a multidisciplinary approach, including surgery, radiation therapy, and systemic chemotherapy. However, treatment of HPC remains a challenge because of

FAQs

What is AT-1 (8-O-acetylharpagide) and where was it isolated from?

AT-1 is an active compound identified as 8-O-acetylharpagide and isolated from Ajuga taiwanensis.

How does AT-1 affect the cell cycle and cell death in FaDu hypopharyngeal cancer cells?

AT-1 induces significant, dose-dependent G2/M phase arrest in FaDu cells and, at high concentrations, triggers necrosis-like fractions and late apoptosis.

Does AT-1 work similarly in periodontal ligament (PDL) cells and does it change radiosensitivity?

AT-1 does not significantly influence cell cycle redistribution or cell death in PDL cells under the same treatment conditions, and it enhances radiosensitivity in FaDu cells rather than PDL cells.

Sep 22, 2026

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