Effects of epoxycarotenoids, β-carotene, and retinoic acid on the differentiation and viability of the leukemia cell line NB4 in vitro
Effects of epoxycarotenoids, β-carotene, and retinoic acid on the differentiation and viability of the leukemia cell line NB4 in vitro
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DOI：
10.1024/0300-9831.69.5.303
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发表时间：
1999-09-01
影响因子：
2.3
通讯作者：
Olson, JA
中科院分区：
文献类型：
--
作者：
Duitsman, PK;Barua, AB;Olson, JA
用3-氯过氧苯甲酸处理β -胡萝卜素，合成了3种β -胡萝卜素（β -car）全反式环氧化合物，即5,6-环氧- β -胡萝卜素（5,6- ec） 5,8-环氧-b-胡萝卜素（5,8- ec）和5,6,5',6'-二环氧- β -胡萝卜素（5,6,5',6'-DEC），并进行了色谱纯化和表征。1 mM化合物对具有急性早幼粒细胞白血病染色体转位t（15;17）特征的NB4细胞诱导分化的相对效价（平均+/- sd）为：RA: 1.35 +/- 0.16, 5,6- ec: 0.29 +/- 0.01, 5,8- ec: 0.22 +/- 0.05, 5,6,5',6'- dec: 0.11 +/- 0.02, β C: 0.09 +/- 0.01，对照组：0.06 +/- 0.01。在其他测试浓度和其他孵育时间中也存在相同的效力顺序。各组分在1 μ M下诱导活性差异的P值为：RA vs. 5,6- ec, < 0.001；5,6- ec vs. 5,8- ec, < 0.01；5,8- ec vs. 5,6,5',6'-DEC, < 0.01；5,6,5',6'-DEC与β - car， < 0.10；β - car与对照组相比，< 0.005。在其他浓度和其他孵育时间的研究中也获得了类似的P值。第4天的活细胞质量与分化程度成反比（r(s) = -1.0）。所有化合物的诱导活性均呈剂量依赖性。因此，β -胡萝卜素的5,6-单环氧化合物在NB4细胞分化中表现出比5,8-单环氧化合物、5,6,5',6'-二环氧化合物或β -胡萝卜素更高的活性，而β -胡萝卜素以前没有作为诱导剂进行过研究。对这些观察结果的可能解释进行了讨论。
Three all-trans epoxides of beta-carotene (beta-Car), namely, 5,6-epoxy-beta-carotene (5,6-EC) 5,8-epoxy-b-carotene (5,8-EC) and 5,6,5',6'-diepoxy-beta-carotene (5,6,5',6'-DEC) were synthesized by treatment of beta-carotene with 3-chloroperoxybenzoic acid, were purified chromatographically, and were characterized. The relative potencies (mean +/- S.D.) of 1 mM compounds in inducing the differentiation of NB4 cells, a cell line that contains the chromosomal transposition t(15;17) characteristic of acute promyelocytic leukemia, after 4 days of incubation were: RA: 1.35 +/- 0.16, 5,6-EC: 0.29 +/- 0.01, 5,8-EC: 0.22 +/- 0.05, 5,6,5',6'-DEC: 0.11 +/- 0.02, beta C: 0.09 +/- 0.01, and the control: 0.06 +/- 0.01. The same order of potencies existed at other concentrations tested and at other incubation times. P values for the differences between the:inducing activities of successive pans of compounds at 1 mu M were: RA vs. 5,6-EC, < 0.001; 5,6-EC vs. 5,8-EC, < 0.01; 5,8-EC vs. 5,6,5',6'-DEC, < 0.01; 5,6,5',6'-DEC vs. beta-Car, < 0.10; beta-Car vs. control, < 0.005. Similar P values were also obtained for studies at other concentrations and at other incubation times. The viable cell mass at 4 days was inversely proportional to the extent of differentiation (r(s) = -1.0). The inducing activities of all compounds were dose-dependent. Thus, the 5,6-monoepoxide of beta-carotene, which has not previously been studied as an inducer, showed higher activity in NB4 cell differentiation than the 5,8-monoepoxide, the 5,6,5',6'-diepoxide, or beta-carotene. Possible explanations of these observations are discussed.