DHMEQ, a new NF-κB inhibitor, induces apoptosis and enhances fludarabine effects on chronic lymphocytic leukemia cells
DHMEQ, a new NF-κB inhibitor, induces apoptosis and enhances fludarabine effects on chronic lymphocytic leukemia cells
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DOI：
10.1038/sj.leu.2404167
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发表时间：
2006-05-01
期刊：
影响因子：
11.4
通讯作者：
Umezawa, K
中科院分区：
文献类型：
--
作者：
Horie, R;Watanabe, M;Umezawa, K
慢性淋巴细胞白血病（CLL）是一种低度恶性淋巴系统肿瘤，无法用常规化疗方式治愈。强的和组成性的核因子κ B（NF-κ B）活化是CLL细胞的特征。我们研究了一种新的NF-κ B抑制剂，去羟甲基表氧喹诺霉素（DHMEQ），对CLL细胞的影响。去羟甲基表氧喹诺霉素完全消除了组成性NF-κ B活性，并诱导CLL细胞凋亡。DHMEQ诱导的细胞凋亡伴随NF-κ B依赖性抗凋亡基因c-IAP、Bfl-1、Bcl-X-L和c-FLIP的下调。去羟甲基表氧喹诺霉素还抑制由CD 40诱导的NF-κ B，增强氟达拉滨介导的CLL细胞凋亡。本研究的结果表明，DHMEQ与氟达拉滨组合抑制组成型和诱导型NF-κ B是治疗CLL的有前景的策略。
Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. Strong and constitutive nuclear factor kappa B (NF-kappa B) activation is a characteristic of CLL cells. We examined the effects of a new NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on CLL cells. Dehydroxymethylepoxyquinomicin completely abrogated constitutive NF-kappa B activity and induced apoptosis of CLL cells. Apoptosis induced by DHMEQ was accompanied by downregulation of NF-kappa B-dependent antiapoptotic genes: c-lAP, Bfl-1, Bcl-X-L and c-FLIP. Dehydroxymethylepoxyquinomicin also inhibited NF-kappa B induced by CD40 and enhanced fludarabine-mediated apoptosis of CLL cells. Results of this study suggest that inhibition of constitutive and inducible NF-kappa B by DHMEQ in combination with fludarabine is a promising strategy for the treatment of CLL.