title: Synergistic inhibition of HTLV-1-infected cell proliferation by combination of cepharanthine and a tetramethylnaphthalene derivative.
abstract: The tetrahydrotetramethylnaphthalene derivative TMNAA has recently been identified as a selective inhibitor of human T-lymphotropic virus type 1 (HTLV-1)-infected T-cell lines and adult T-cell leukemia (ATL) cells but not of uninfected T-cell lines and peripheral blood mononuclear cells (PBMCs). Although the target molecule of TMNAA is still unknown, it does not inhibit nuclear factor-κB (NF-κB) activity. Therefore, TMNAA was examined for its inhibitory effect on the cell proliferation in combination with the NF-κB inhibitor cepharanthine. Synergism was observed for the combination, in inhibiting the proliferation of HTLV-1-infected T-cell lines. Although TMNAA alone did not induce the apoptosis of HTLV-1-infected T-cell lines, it strongly enhanced their apoptosis induced by cepharanthine. Thus, TMNAA may have potential as a therapeutic agent against ATL either alone or in combination with cepharanthine, which is clinically used as an anti-inflammatory drug in Japan.
authors: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
authors: Masaaki
authors: M
authors: Toyama
authors: Takayuki
authors: T
authors: Hamasaki
authors: Tomofumi
authors: T
authors: Uto
authors: Hiroshi
authors: H
authors: Aoyama
authors: Mika
authors: M
authors: Okamoto
authors: Yuichi
authors: Y
authors: Hashmoto
authors: Masanori
authors: M
authors: Baba
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D002461:Cell Line, Transformed; D004357:Drug Synergism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000821:virology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D052117:Benzodioxoles
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D016328:NF-kappa B; D013764:Tetrahydronaphthalenes; C006947:cepharanthine; D052117:Benzodioxoles