Novel valproic acid derivatives with potent differentiation-inducing activity in myeloid leukemia cells

被引：31

作者：

Deubzer, Hedwig

Busche, Barbara

Roenndahl, Gabi

Eikel, Daniel

Michaelis, Martin

Cinatl, Jindrich

Schulze, Sandra

Nau, Heinz

Witt, Olaf ^{[1
]}

机构：

[1] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, D-6900 Heidelberg, Germany

[2] Univ Heidelberg, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[3] Univ Gottingen, D-3400 Gottingen, Germany

[4] Sch Vet Med, Inst Food Toxicol & Chem Anal, Hannover, Germany

[5] Univ Frankfurt, Inst Med Virol, D-6000 Frankfurt, Germany

来源：

LEUKEMIA RESEARCH | 2006年 / 30卷 / 09期

关键词：

VPA; differentiation; HDAC; leukemia; K562; HL60; p21(Cip/Waf); HISTONE DEACETYLASE INHIBITORS; FETAL-HEMOGLOBIN EXPRESSION; HUMAN NEUROBLASTOMA-CELLS; IN-VITRO; TRANSFORMED-CELLS; SODIUM VALPROATE; INDUCTION; PROLIFERATION; ANALOGS; CANCER;

D O I：

10.1016/j.leukres.2006.01.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The anti-epileptic drug valproic acid harbors anti-tumoral activity in solid and leukemic tumor cell models and is currently evaluated in clinical trials. However, the plasma trough concentrations obtained in patients by common anti-epileptic dose regimens are below concentrations required for exerting anti-tumor effects in vitro. Here, we describe the identification of three novel valproic acid derivatives with superior differentiation-inducing and anti-proliferative activities in K562 bcr/abl-positive chronic myeloid leukemia cells and HL60 promyelocytic leukemia cells at achievable therapeutic VPA concentrations. These compounds reveal potent inhibition of histone deacetylase activity, induction of P21(Cip/Waf) expression as well as low toxicity on CD34(+) bone marrow cells. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1167 / 1175

页数：9

共 47 条

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