Sokoloski J A, Shyam K, Sartorelli A C
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Oncol Res. 1997;9(1):31-9.
Previous studies have shown that an antisense phosphorothioate oligonucleotide to the Rel A subunit of NF- kappa B, as well as vitamin E and related antioxidants, significantly enhanced the differentiation of HL-60 leukemia cells when combined with low levels of 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3) an effect accompanied by a marked inhibition of the transcription factor, NF-kappa B. Curcumin, a potent inhibitor of tumor promotion and of tumor cell growth, has also been shown to have antioxidant properties and to inhibit NF-kappa b. to ascertain whether curcumin would also enhance the differentiation of HL-60 leukemia cells produced by vitamin D3, presumably by interfering with NF- kappa B activity, the effects of curcumin on the differentiation of HL-60 cells produced by low levels of vitamin D3 were measured. Curcumin used alone did not produce a significant degree of differentiation of HL-60 cells; however, this agent markedly enhanced the expression of differentiation markers induced by low levels of vitamin D3. Curcumin also increased the differentiation of HL-60 cells when combined with vitamin D analogues (1,25-dihydroxy-16-ene-23-yne vitamin D3 and 1,25-dihydroxy-16-ene vitamin D3) that share the receptor binding properties of vitamin D3, whereas as vitamin D analogue (1,25-dihydroxy-16,23-diene vitamin D3) that caused significant calcium mobilization, but was less effective than vitamin d3 in binding the receptor, did not cause the differentiation of HL-60 cells in the presence or absence of curcumin. Several dietary compounds structurally related to curcumin (i.e., caffeic acid, chlorogenic acid, and ferulic acid) did not increase the differentiation of HL-60 cells produced by vitamin D3. However, the more lipophilic ethyl of ferulic and caffeic acid were capable of inducing the differentiation of HL-60 cells, as well as enhancing the maturation produced by vitamin D3. Curcumin caused a marked reduction in NF-kappa B activity in nuclear extracts of HL-60 cells exposed to this agent in the presence or absence of vitamin D3, supporting the possibility that NF-kappa B may be a factor in the regulation of the state of differentiation of leukemia cells.
先前的研究表明，针对核因子κB（NF-κB）的Rel A亚基的反义硫代磷酸酯寡核苷酸，以及维生素E和相关抗氧化剂，与低水平的1α,25-二羟基维生素D3（维生素D3）联合使用时，能显著增强HL-60白血病细胞的分化，这种作用伴随着转录因子NF-κB的明显抑制。姜黄素是一种有效的肿瘤促进和肿瘤细胞生长抑制剂，也已被证明具有抗氧化特性并能抑制NF-κB。为了确定姜黄素是否也能增强维生素D3诱导的HL-60白血病细胞的分化，推测是通过干扰NF-κB活性，检测了姜黄素对低水平维生素D3诱导的HL-60细胞分化的影响。单独使用姜黄素不会使HL-60细胞产生显著程度的分化；然而，该试剂显著增强了低水平维生素D3诱导的分化标志物的表达。当姜黄素与具有维生素D3受体结合特性的维生素D类似物（1,25-二羟基-16-烯-23-炔维生素D3和1,25-二羟基-16-烯维生素D3）联合使用时，也增加了HL-60细胞的分化，而作为一种能引起显著钙动员但在结合受体方面比维生素D3效果差的维生素D类似物（1,25-二羟基-16,23-二烯维生素D3），在有或没有姜黄素的情况下都不会引起HL-60细胞的分化。几种与姜黄素结构相关的膳食化合物（即咖啡酸、绿原酸和阿魏酸）不会增加维生素D3诱导的HL-60细胞的分化。然而，阿魏酸和咖啡酸的亲脂性更强的乙酯能够诱导HL-60细胞的分化，以及增强维生素D3产生的成熟作用。在有或没有维生素D3的情况下，姜黄素都会使暴露于该试剂的HL-60细胞核提取物中的NF-κB活性显著降低，这支持了NF-κB可能是白血病细胞分化状态调节因子的可能性。
