Blocking NF-κB as a potential strategy to treat adult T-cell leukemia/lymphoma
Blocking NF-κB as a potential strategy to treat adult T-cell leukemia/lymphoma
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DOI：
10.1358/dnp.2006.19.4.985934
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发表时间：
2006-05-01
影响因子：
--
通讯作者：
Umezawa, Kazuo
中科院分区：
文献类型：
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作者：
Horie, Ryouichi;Watanabe, Toshiki;Umezawa, Kazuo
成人T细胞白血病/淋巴瘤（ATL）是一种对化疗耐药的致命性T细胞白血病/淋巴瘤，由人类T细胞白血病/淋巴瘤病毒I型（HTLV-1）引起，即使在初始传播的50年临床潜伏期后也会发生。组成性激活的核因子KB（NF-κ B）似乎是ATL细胞中观察到的异常生长和细胞因子基因表达的分子基础，从而作为治疗ATL的理想靶点。去羟甲基表氧喹诺霉素（DHMEQ）是一种新型的NF-κ B抑制剂，它是环氧喹诺霉素C的5-去羟甲基衍生物，具有类似于泛环氧酮的4-羟基-5，6-环氧环己烯酮结构。这种独特的化合物在NF-κ B易位到细胞核中起作用。脱羟甲基表氧喹诺霉素抑制ATL细胞中的NF-κ B活化并诱导凋亡性细胞死亡。此外，DHMEQ在体外选择性靶向病毒携带者外周血中的HTLV-1感染细胞，导致感染细胞数量减少。我们的结论是，阻断NF-κ B是治疗和预防ATL的潜在策略。DHMEQ作为一种有效的NF-κ B抑制剂，是将这一策略转化为临床药物的一种有前途的化合物。(c)2006年，《科学》杂志。All rights reserved.
Adult T-cell leukemia/lymphoma (ATL), a fatal T-cell leukemia/lymphoma resistant to chemotherapy, is caused by human T-cell leukemia/lymphoma virus type I (HTLV-1), occurring even after 50 years of clinical latency from initial transmission. Constitutively activated nuclear factor KB (NF-KB) appears to be a molecular basis for the aberrant growth and cytokine gene expression observed in ATL cells, thereby serving as an ideal target in the treatment of ATL. Dehydroxymethylepoxyquinomicin (DHMEQ) is a new NF-KB inhibitor that is a 5-dehydroxymethyl derivative of epoxyquinomicin C, having a 4-hydroxy-5,6-epoxycyclohexenone structure similar to panepoxydone. This unique compound acts in the translocation of NF-KB into the nucleus. Dehydroxymethylepoxyquinomicin inhibits NF-KB activation in ATL cells and induces apoptotic cell death. In addition, DHMEQ selectively targets HTLV-1-infected cells in the peripheral blood of virus carriers in vitro, resulting in a decreased number of infected cells. We have concluded that blocking NF-KB is a potential strategy for the treatment and prevention of ATL. As a potent NF-KB inhibitor, DHMEQ is a promising compound for translating this strategy into clinical medicine. (c) 2006 Prous Science. All rights reserved.