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Updated: Jan 30, 2026
Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
Published on: February 18, 2014
Guanabenz Acetate Induces Endoplasmic Reticulum Stress-Related Cell Death in Hepatocellular Carcinoma Cells
Hyo Jeong Kang1, Hyang Sook Seol2, Sang Eun Lee2
1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Background:
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods:
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results:
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions:
Guanabenz acetate induces endoplasmic reticulum stress-related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.
Insights
Guanabenz acetate, an existing antihypertensive drug, effectively targets hepatocellular carcinoma (HCC) by inducing cell death. This study highlights its potential as a novel repositioned cancer therapeutic for HCC patients.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Chemotherapeutic development for advanced hepatocellular carcinoma (HCC) faces significant challenges.
- Patient-derived preclinical models offer a promising avenue for accelerating drug discovery in HCC.
Purpose of the Study:
- To screen for novel therapeutic agents for hepatocellular carcinoma (HCC).
- To evaluate the efficacy and mechanism of action of candidate drugs in HCC models.
Main Methods:
- High-throughput screening of 252 drugs from the Prestwick Chemical Library against four primary HCC cultures and six HCC cell lines.
- Analysis of drug efficacy using cell viability and cell cycle assays.
- Investigation of mechanisms of action via western blotting.
Main Results:
- Guanabenz acetate, an antihypertensive medication, was identified as a potential anti-cancer agent for HCC.
- Guanabenz acetate demonstrated reduced HCC cell viability by inducing apoptosis and autophagy.
- The drug inhibited growth arrest and DNA damage-inducible protein 34, leading to cell cycle arrest via increased eIF2α phosphorylation and ATF4 activation.
Conclusions:
- Guanabenz acetate induces endoplasmic reticulum stress-related cell death in HCC.
- Guanabenz acetate shows potential for repositioning as an anti-cancer therapeutic for HCC patients.
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