A small molecule that selectively inhibits the growth of Epstein-Barr virus-latently infected cancer cells
Ying Li,
Shujuan Du,
Kun Zhou,
Yulin Zhang,
Xiaoting Chen,
Caixia Zhu,
Yuping Jia,
Yuyan Wang,
Daizhou Zhang,
Fang Wei,
Yin Tong,
Qiliang Cai
Affiliations
Ying Li
Division of Hematology, Shanghai First People’s Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China
Shujuan Du
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Kun Zhou
Division of Hematology, Shanghai First People’s Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China
Yulin Zhang
Division of Hematology, Shanghai First People’s Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China
Xiaoting Chen
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Caixia Zhu
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Yuping Jia
Shandong Academy of Pharmaceutical Sciences, Jinan 250100, P.R. China
Yuyan Wang
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Daizhou Zhang
Shandong Academy of Pharmaceutical Sciences, Jinan 250100, P.R. China; Corresponding author
Fang Wei
Division of Hematology, Shanghai First People’s Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China; Corresponding author
Yin Tong
Division of Hematology, Shanghai First People’s Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China; Corresponding author
Qiliang Cai
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China; Corresponding author
Summary: Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth in vitro by high-throughput screening. Among them, cetrimonium bromide (CetB) was identified to selectively inhibit the growth of different EBV-infected B lymphoma cell lines. Importantly, CetB reduced EBNA1 protein stability, activated G1 arrest and early apoptosis of EBV-latently infected cells without viral lytic reactivation, which leads to dramatically inhibit colony formation and tumor growth of EBV-infected cells in vitro and in vivo, and significantly prolong the survival of tumor-bearing mice. Overall, these findings demonstrate that CetB acts as a highly selective inhibitor of the growth of EBV-infected cells and has the potential for further development of effective therapeutic strategies specific against EBV-associated cancers.
