title: Synergistic effects by combination of ganciclovir and tricin on human cytomegalovirus replication in vitro.
abstract: It has been demonstrated as the first report that combination treatment with ganciclovir (GCV) and tricin (4',5,7-trihydroxy-3',5' -dimethoxyflavone), a derivative of Sasa albo-marginata, after human cytomegalovirus (HCMV) infection has synergistic effects on both infectious virus production and HCMV DNA synthesis in the human embryonic fibroblast cell line MRC-5. In this paper, we examined the anti-HCMV effects of GCV plus various concentrations of tricin, and tricin plus various concentrations of GCV in MRC-5 cells. We found that expression of the HCMV UL54 gene was significantly inhibited by combination of GCV with tricin when compared with GCV mono-treatment. These results suggest that tricin is a novel compound for combination therapy with GCV against HCMV replication. In addition, reduced-dose combination therapy may provide a direction for treatment in patients with HCMV infection while reducing drug toxicity.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Suda
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sadanari
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Hououdou Co. Ltd., 4-3-2 Ebara, Shinagawa-ku, Tokyo 142-0063, Japan.
authors.forename: Yuuzo
authors.initials: Y
authors.lastname: Tuchida
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. Electronic address: t-murayama@hokuriku-u.ac.jp.
authors.forename: Tsugiya
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology*; D004261:DNA Replication / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000821:virology; D005419:Flavonoids / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D008297:Male; D031787:Sasa / Q000737:chemistry; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; C017769:tricin; D004259:DNA-Directed DNA Polymerase; D015774:Ganciclovir
keywords: Anti-cytomegalovirus activity; Combination therapy; Ganciclovir; Synergistic effects; Tricin; UL54