dehydroxymethylepoxyquinomicin has been researched along with Leukemia--T-Cell* in 2 studies
2 other study(ies) available for dehydroxymethylepoxyquinomicin and Leukemia--T-Cell
| Article | Year |
|---|---|
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. Topics: Adult; Animals; Apoptosis; Benzamides; beta 2-Microglobulin; Cell Line, Tumor; Cyclohexanones; Gene Products, tax; Human T-lymphotropic virus 1; Humans; Leukemia, T-Cell; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; NF-kappa B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Analysis; Tumor Burden; Xenograft Model Antitumor Assays | 2007 |
Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia.
Human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia (ATL), a fatal T-cell leukemia resistant to chemotherapy, after more than 50 years of clinical latency from transmission through breast-feeding. Polyclonal expansion of virus-infected T cells predisposes them to transformation. Constitutive activation of nuclear factor-kappaB (NF-kappaB) in the leukemic cells is essential for their growth and survival. Blocking NF-kappaB has been shown to be a potential strategy to treat ATL. We tested this approach using a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), and also examined its application to chemoprevention by selective purging of the HTLV-1-infected cells. DHMEQ inhibited NF-kappaB activation in primary ATL cells and cell lines derived from them and induced apoptotic cell death. NF-kappaB inhibition down-regulated expression of genes involved in antiapoptosis or cell-cycle progression. DHMEQ protected severe combined immunodeficiency (SCID) mice inoculated with HTLV-1-transformed cells from death. In addition, DHMEQ selectively targeted HTLV-1-infected cells in the peripheral blood of virus carriers in vitro, resulting in a decreased number of infected cells. We conclude that NF-kappaB is a potential molecular target for treatment and prevention of ATL. As a potent NF-kappaB inhibitor, DHMEQ is a promising compound allowing the translation of this strategy into clinical medicine. Topics: Animals; Antineoplastic Agents; Apoptosis; Benzamides; Caspases; Cell Cycle; Cell Line; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; Cyclohexanones; Dose-Response Relationship, Drug; Down-Regulation; Gene Expression Regulation, Neoplastic; Genes, Reporter; Human T-lymphotropic virus 1; Humans; Immunoblotting; Immunohistochemistry; Jurkat Cells; K562 Cells; Leukemia-Lymphoma, Adult T-Cell; Leukemia, T-Cell; Leukocytes, Mononuclear; Male; Mice; Mice, SCID; Microscopy, Fluorescence; Molecular Weight; NF-kappa B; Proviruses; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; Time Factors; Tumor Suppressor Protein p53 | 2005 |