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Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones

Leukemia volume 18, pages 1413–1419 (2004)Cite this article

Abstract

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, α-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.

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Acknowledgements

This work was supported in part by Grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Saitama Cancer Center Research Institute, Saitama, Japan

    Y Ishii & Y Honma

  2. Institute of Biological Science, Tsukuba University, Ibaraki, Japan

    Y Ishii & S Sakai

  3. Graduate School of Agricultural Science, Tohoku University, Sendai, Japan

    H Kiyota

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  1. Y Ishii
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  4. Y Honma
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Correspondence to Y Honma.

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Supplementary information accompanies this paper on the Cell Death and Differentiation website: http://www.nature.com/cdd

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Ishii, Y., Kiyota, H., Sakai, S. et al. Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones. Leukemia 18, 1413–1419 (2004). https://doi.org/10.1038/sj.leu.2403421

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