Antrocinol-mediated downregulation of ATG5 induces autophagy-dependent cell death and activates the unfolded protein response through PERK/CHOP signaling in lenvatinib-resistant hepatocellular carcinoma cells
This study provides the first evidence that Antrocinol, a novel hydroxylated derivative of antrocin, synergises with Lenvatinib to exert anti-proliferative effects on Lenvatinib-resistant HCC cells. Our results indicate that Antrocinol may enhance chemosensitivity in HCC by activating the unfolded protein response (UPR) pathway, specifically through the PERK/CHOP axis, and promoting autophagy-dependent cell death. These findings suggest that autophagy acts as a tumor-suppressive mechanism in HCC, with potential therapeutic implications for overcoming drug resistance.
Authors
- Chi‐Tai Yeh (ORCID: https://orcid.org/0000-0001-5189-9755)
- Ming‐Shou Hsieh
- Tung-Yao Tsai
- Kuang‐Tai Kuo
- Vijesh Kumar Yadav (ORCID: https://orcid.org/0000-0002-2679-1205)
- Yi‐Chiao Cheng (ORCID: https://orcid.org/0000-0001-8317-1339)
- Shiue‐Wei Lai (ORCID: https://orcid.org/0000-0003-2928-5401)
- Yew‐Min Tzeng (ORCID: https://orcid.org/0000-0002-9360-2072)
Institutions
- Tri-Service General Hospital (TW)
- National Taitung University (TW)
- Taipei Medical University Hospital (TW)
- China Medical University Hospital (TW)
- Taipei Medical University-Shuang Ho Hospital (TW)
- National Defense Medical Center (TW)
Publication Details
- Journal
- European Journal of Pharmacology
- Published
- 2025-09-03
- DOI
- https://doi.org/10.1016/j.ejphar.2025.178115
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Council
- National Taiwan University Hospital