title: Inhibition of Vpr-induced cell cycle abnormality by quercetin: a novel strategy for searching compounds targeting Vpr.
abstract: Vpr, an accessory gene product of HIV-1 which induces cell cycle abnormality leading to the increased HIV replication, is supposed to be a possible target for anti-AIDS drugs. We recently established a cell line (MIT-23) in which Vpr-induced cell cycle perturbation could be manipulated by a tetracycline promoter. Here, we screened anti-Vpr activity in 27 kinds of herb drugs using MIT-23 cells. One of the extracts prepared from Houttuyniae herba showed an inhibitory activity. Quercetin (QCT), a compound of this crude drug, efficiently inhibited Vpr function without affecting its expression. Furthermore, data suggested that Vpr-induced transcription from HIV-LTR was considerably abrogated by QCT. These data indicate that QCT, a flavonoid previously reported to inhibit HIV replication, also targets Vpr, implicating that MIT-23 cell provides a novel strategy for screening compounds possessing anti-Vpr activity which would be in turn utilized for clarifying the mechanism of Vpr function.
authors.affiliation: Department of Intractable Diseases, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimura
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Asada
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: K
authors.initials: K
authors.lastname: Hatake
authors.forename: F
authors.initials: F
authors.lastname: Takaku
authors.forename: Y
authors.initials: Y
authors.lastname: Ishizaka
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015870:Gene Expression; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D016334:Genes, vpr; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D008517:Phytotherapy; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D016336:Gene Products, vpr; D006727:Hormone Antagonists; D054325:vpr Gene Products, Human Immunodeficiency Virus; D015735:Mifepristone; D011794:Quercetin