title: Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with tax-deficient adult T-cell leukemia-derived cell lines.
abstract: Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type I (HTLV-I), which induces nuclear factor-kappaB (NF-kappaB), a molecule central to the ensuing neoplasia. The NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has been shown to inhibit NF-kappaB activation in Tax-expressing HTLV-I-infected cells. In this study, we used NOD/SCID beta2-microglobulin(null) mice to show that intraperitoneal inoculation with Tax-deficient ATL cell lines caused rapid death, whereas DHMEQ-treated mice survived. Furthermore, DHMEQ treatment after subcutaneous inoculation inhibited the growth of transplanted ATL cells. These results demonstrate that DHMEQ has therapeutic efficacy on ATL cells, regardless of Tax expression.
authors.affiliation: Division of Microbiology and Genetics, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. ohsugi@gpo.kumamoto-u.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohsugi
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Takaomi
authors.initials: T
authors.lastname: Ishida
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Horie
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003512:Cyclohexanones / Q000494:pharmacology* / Q000627:therapeutic use; D016356:Gene Products, tax / Q000172:deficiency* / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015458:Leukemia, T-Cell / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays / Q000379:methods*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
chemical_list: D001549:Benzamides; D003512:Cyclohexanones; D016356:Gene Products, tax; D016328:NF-kappa B; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; C464444:dehydroxymethylepoxyquinomicin