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Antitumor Effect of Sugar-Modified Cytosine Nucleosides on Growth of Adult T-Cell Leukemia Cells in Mice

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Title: Antitumor Effect of Sugar-Modified Cytosine Nucleosides on Growth of Adult T-Cell Leukemia Cells in Mice
Authors: Maeda, Naoyoshi Browse this author →KAKEN DB
Matsuda, Akira Browse this author →KAKEN DB
Otsuguro, Satoko Browse this author
Takahashi, Masahiko Browse this author
Fujii, Masahiro Browse this author
Maenaka, Katsumi Browse this author →KAKEN DB
Keywords: adult T-cell leukemia
NOG mice
Issue Date: 5-Nov-2020
Publisher: MDPI
Journal Title: Vaccines
Volume: 8
Issue: 4
Start Page: 658
Publisher DOI: 10.3390/vaccines8040658
Abstract: Adult T-cell leukemia (ATL) is a CD4(+) T-cell neoplasm caused by human T-cell leukemia virus type I. As the prognosis for patients with ATL remains extremely poor due to resistance to conventional chemotherapy regimens, introduction of novel therapeutic agents is needed. Previous studies have reported that nucleosides 2 '-deoxy-2 '-methylidenecytidine (DMDC) and its derivative 2 '-deoxy-2 '-methylidene-5-fluorocytidine (FDMDC) exhibit antitumor activities in T-cell acute lymphoblastic leukemia (T-ALL) and solid tumor cell lines. Another nucleoside, 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)cytosine (cytarazid), is considered a therapeutic drug with antitumor activity in human solid tumors. In this study, we investigated the effects of these nucleosides on cell growth in vitro and in vivo using relevant leukemia cell lines and NOD/Shi-scid, IL-2Rg(null) (NOG) mice, respectively. The nucleosides demonstrated significant cytotoxic effects in ATL and T-ALL cell lines. Intraperitoneal administration of FDMDC and DMDC into tumor-bearing NOG mice resulted in significant suppression of tumor growth without lethal side effects. Our findings support a therapeutic application of these nucleosides against tumor progression by targeting DNA polymerase-dependent DNA synthesis in patients with ATL.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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