在NB4、NB4-R2和原发性急性早幼粒细胞白血病细胞中，在不存在或存在全反式维甲酸和三氧化二砷的情况下，(+)α-生育酚琥珀酸酯诱导细胞凋亡。

Apoptosis induction by (+)alpha-tocopheryl succinate in the absence or presence of all-trans retinoic acid and arsenic trioxide in NB4, NB4-R2 and primary APL cells.

作者信息

Freitas Rosana Aparecida, Silva dos Santos Guilherme Augusto, Gimenes Teixeira Hamilton Luiz, Scheucher Priscila Santos, Lucena-Araujo Antonio Roberto, Lima Ana Sílvia Gouveia, Abreu e Lima Rodrigo Siqueira, Garcia Aglair Bergamo, Jordão Alceu Afonso, Falcão Roberto Passetto, Vannucchi Hélio, Rego Eduardo Magalhães

机构信息

Hematology Division, Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, SP, Brazil.

出版信息

Leuk Res. 2009 Jul;33(7):958-63. doi: 10.1016/j.leukres.2008.09.035. Epub 2008 Nov 14.

DOI:10.1016/j.leukres.2008.09.035

PMID:19013639

Abstract

We analyzed the effect of (+)alpha-tocopheryl succinate (alpha-TOS) alone or associated with arsenic trioxide (ATO) or all-trans retinoid acid (ATRA) in acute promyelocytic leukemia (APL). alpha-TOS-induced apoptosis in APL clinical samples and in ATRA-sensitive (NB4) and ATRA-resistant (NB4-R2) APL cell lines. The effective dose 50% (ED-50) was calculated to be 71 and 58muM, for NB4 and NB4-R2, respectively. alpha-TOS neither induced nor modified ATRA-induced differentiation of APL cells, and did not affect the proliferation and differentiation of normal CD34(+) hematopoietic progenitors in methylcellulose assays. alpha-TOS exerted a moderate antagonistic effect to ATO-induced apoptosis when treatment was done simultaneously but when alpha-TOS was added 24h after ATO, an additive effect was observed. Our results support the concept of alpha-TOS as an anti-leukemic compound which spares normal hematopoiesis.

摘要

我们分析了琥珀酸（+）α-生育酚（α-TOS）单独使用或与三氧化二砷（ATO）或全反式维甲酸（ATRA）联合使用对急性早幼粒细胞白血病（APL）的影响。α-TOS可诱导APL临床样本以及对ATRA敏感的（NB4）和对ATRA耐药的（NB4-R2）APL细胞系发生凋亡。计算得出，NB4和NB4-R2的半数有效剂量（ED-50）分别为71μM和58μM。α-TOS既不诱导也不改变ATRA诱导的APL细胞分化，并且在甲基纤维素试验中不影响正常CD34（+）造血祖细胞的增殖和分化。当同时进行处理时，α-TOS对ATO诱导的凋亡具有中等程度的拮抗作用，但当在ATO处理24小时后添加α-TOS时，则观察到相加作用。我们的结果支持α-TOS作为一种不影响正常造血功能的抗白血病化合物的概念。