title: Selective inhibition of HTLV-1-infected cell proliferation by a novel tetramethylnaphthalene derivative.
abstract: Adult T-cell leukemia (ATL) is caused by infection with human T-lymphotropic virus type 1 (HTLV-1). A novel tetramethylnaphthalene derivative, TMNAA, selectively inhibited the proliferation of various HTLV-1-infected cells, including ATL cell lines and peripheral blood mononuclear cells (PBMCs) from ATL patients. In contrast, the proliferation of uninfected cell lines and PBMCs from healthy donors was hardly affected by the compound. Cell-cycle analysis revealed that TMNAA increased the population of the G0/G1 phase and reduced that of the S phase in HTLV-1-infected cells. TMNAA was found to suppress the phosphorylation of retinoblastoma protein and the expression of cyclin-dependent kinase 4 in HTLV-1-infected cells. Furthermore, the inhibition of cell proliferation was partially annihilated by removing the compound. These results indicate that TMNAA exerts selective inhibition of HTLV-1-infected cells through a novel mechanism, presumably modulating cell cycle regulatory proteins associated with the G0/G1 phase.
authors: Division of Antiviral Chemotherapy, Center for Chronic Viral Disease, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
authors: Takayuki
authors: T
authors: Hamasaki
authors: Masaaki
authors: M
authors: Toyama
authors: Hiroshi
authors: H
authors: Aoyama
authors: Yohann
authors: Y
authors: White
authors: Mika
authors: M
authors: Okamoto
authors: Naomichi
authors: N
authors: Arima
authors: Yuichi
authors: Y
authors: Hashimoto
authors: Masanori
authors: M
authors: Baba
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D004789:Enzyme Activation; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D009281:Naphthalenes / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D009281:Naphthalenes; D016160:Retinoblastoma Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D020169:Caspases