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1 "Primary cell culture"
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Original Article
Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells
Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu
J Pathol Transl Med. 2019;53(2):94-103.   Published online January 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.01.14
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  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary Material
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.

Citations

Citations to this article as recorded by  
  • Current trends and future prospects of drug repositioning in gastrointestinal oncology
    Nayeralsadat Fatemi, Mina Karimpour, Hoda Bahrami, Mohammad Reza Zali, Vahid Chaleshi, Andrea Riccio, Ehsan Nazemalhosseini-Mojarad, Mehdi Totonchi
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • The integrated stress response in cancer progression: a force for plasticity and resistance
    Caleb L. Lines, Morgan J. McGrath, Tanis Dorwart, Crystal S. Conn
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma
    Jiacheng Wu, Shan Qiao, Yien Xiang, Menying Cui, Xiaoxiao Yao, Ruixin Lin, Xuewen Zhang
    Biomedicine & Pharmacotherapy.2021; 142: 112005.     CrossRef
  • The two faces of the Integrated Stress Response in cancer progression and therapeutic strategies
    Eugenia Licari, Luis Sánchez-del-Campo, Paola Falletta
    The International Journal of Biochemistry & Cell Biology.2021; 139: 106059.     CrossRef
  • Repurposing of Guanabenz acetate by encapsulation into long-circulating nanopolymersomes for treatment of triple-negative breast cancer
    Yusuf A. Haggag, Mohamed Yasser, Murtaza M. Tambuwala, Suleiman S. El Tokhy, Mohammad Isreb, Ahmed A. Donia
    International Journal of Pharmaceutics.2021; 600: 120532.     CrossRef
  • Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases
    Marina S. Gorbatyuk, Christopher R. Starr, Oleg S. Gorbatyuk
    Progress in Retinal and Eye Research.2020; 79: 100860.     CrossRef
  • Delineating the role of eIF2α in retinal degeneration
    Christopher R. Starr, Marina S. Gorbatyuk
    Cell Death & Disease.2019;[Epub]     CrossRef
  • Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri
    Areeba Anwar, Mohammad Ridwane Mungroo, Ayaz Anwar, William J. Sullivan, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
    ACS Infectious Diseases.2019; 5(12): 2039.     CrossRef

J Pathol Transl Med : Journal of Pathology and Translational Medicine