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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Apoptosis / drug effects
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Benzamides / pharmacology*
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Benzamides / therapeutic use
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Cell Line, Tumor
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Cyclohexanones / pharmacology*
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Cyclohexanones / therapeutic use
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Gene Products, tax / deficiency*
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Gene Products, tax / genetics
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Human T-lymphotropic virus 1 / genetics
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Human T-lymphotropic virus 1 / metabolism
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Humans
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Leukemia, T-Cell / pathology
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Leukemia, T-Cell / prevention & control*
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Leukemia, T-Cell / virology
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Mice
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Mice, Inbred NOD
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Mice, Knockout
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Mice, SCID
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Analysis
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Tumor Burden
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Xenograft Model Antitumor Assays / methods*
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beta 2-Microglobulin / genetics
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beta 2-Microglobulin / metabolism
Substances
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Benzamides
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Cyclohexanones
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Gene Products, tax
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NF-kappa B
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RNA, Messenger
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beta 2-Microglobulin
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dehydroxymethylepoxyquinomicin