Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones
Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones
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DOI：
10.1038/sj.leu.2403421
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发表时间：
2004-08-01
期刊：
影响因子：
11.4
通讯作者：
Honma, Y
中科院分区：
文献类型：
--
作者：
Ishii, Y;Kiyota, H;Honma, Y
一些植物生长和分化的调节剂已被证明可以诱导几种人髓性白血病细胞的分化，并且可能作为分化诱导剂有效控制急性髓性白血病细胞。在这项研究中，检查了茉莉酸对人骨髓性白血病细胞的生长抑制和分化诱导作用。用茉莉酸甲酯（MJ）及其衍生物培养几种骨髓性白血病细胞。通过硝基蓝四唑还原活性、形态变化、α-萘乙酸酯酶活性和分化相关表面抗原的表达来确定细胞分化。 MJ 诱导 HL-60 细胞的单核细胞和粒细胞分化。 MJ 在引起骨髓单核细胞分化之前激活细胞中的丝裂原激活蛋白激酶 (MAPK)。 MAPK 激活对于 MJ 诱导的分化是必需的，因为 MAPK 激酶抑制剂 PD98059 抑制 MJ 诱导的分化。 MJ 还诱导其他人类白血病细胞系的分化。在4,5位引入双键大大增强了MJ的分化诱导活性。 MJ 及其衍生物可有效诱导某些粒单核细胞白血病细胞的分化。一种新的衍生物是一种特别有前途的治疗白血病的治疗剂。
Some regulators of plant growth and differentiation have been shown to induce the differentiation of several human myeloid leukemia cells, and might be effective as differentiation inducers to control acute myelogenous leukemia cells. In this study, the growth-inhibiting and differentiation-inducing effects of jasmonates on human myeloid leukemia cells were examined. Several myeloid leukemia cells were cultured with methyl jasmonate (MJ) and its derivatives. Cell differentiation was determined by nitroblue tetrazolium-reducing activity, morphological changes, alpha-naphthyl acetate esterase activity and expression of differentiation-associated surface antigens. MJ induced both monocytic and granulocytic differentiation of HL-60 cells. MJ activated mitogen-activated protein kinase (MAPK) in the cells before causing myelomonocytic differentiation. MAPK activation was necessary for MJ-induced differentiation, since PD98059, an inhibitor of MAPK kinase, suppressed the differentiation induced by MJ. MJ also induced the differentiation of other human leukemia cell lines. Introduction of a double bond at the 4,5-position greatly enhanced the differentiation-inducing activity of MJ. MJ and its derivatives potently induce the differentiation of some myelomonocytic leukemia cells. One novel derivative is a particularly promising therapeutic agent for the treatment of leukemia.