Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with tax-deficient adult T-cell leukemia-derived cell lines.
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.
Ohsugi
Takeo
T
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
Kumasaka
Toshio
T
Okada
Seiji
S
Ishida
Takaomi
T
Yamaguchi
Kazunari
K
Horie
Ryouichi
R
Watanabe
Toshiki
T
Umezawa
Kazuo
K
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
D001549:Benzamides; D003512:Cyclohexanones; D016356:Gene Products, tax; D016328:NF-kappa B; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; C464444:dehydroxymethylepoxyquinomicin