title: Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines.
abstract: Lytic induction of latent Kaposi's sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of FDA-approved drugs. Lytic induction of latent KSHV by three compounds was verified by the significant induction of lytic genes and subsequent production of infectious KSHV. Importantly, lytic induction by three compounds was much more efficient than that by sodium butyrate, a well-characterized inducer of KSHV lytic cycle. Mechanistically, the anthracyclines caused lytic induction of KSHV through apoptosis induced by their DNA intercalation rather than topoisomerase II inhibition. Consequently, our results clearly demonstrated a role of anthracyclines as effective lytic inducers of KSHV and also provided a molecular basis of their use for efficient treatment of diseases associated with KSHV infection.
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea. College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Jaehyung
authors.initials: J
authors.lastname: Song
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea. Department of Medical Biotechnology, Soonchunhyang University, Asan, Republic of Korea.
authors.forename: Kwangman
authors.initials: K
authors.lastname: Choi
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea. Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Hyeongki
authors.initials: H
authors.lastname: Kim
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea.
authors.forename: Miri
authors.initials: M
authors.lastname: Choi
authors.affiliation: International Cooperation Office, Ministry of Food and Drug Safety, Cheongwon, Chungbuk, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Virus Research and Testing Group, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Chonsaeng
authors.initials: C
authors.lastname: Kim
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Song
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, and Institute for Microorganisms, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyojeung
authors.initials: H
authors.lastname: Kang
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Back
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea. Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017930:Genes, Reporter; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D057166:High-Throughput Screening Assays; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic