Abstract
Jasmonates are potent lipid regulators in plants that play pivotal roles in their biological activities. Methyl jasmonate (MJ) is very effective at inducing the myelomonocytic differentiation of human myeloid leukemia HL-60 cells. We examined the gene expression profiles associated with exposure to MJ using cDNA microarrays, and compared the results with those obtained with other inducers of differentiation, such as all-trans retinoic acid (ATRA), 1α,25-dihydroxyvitamin D3 (VD3), isopentenyladenine (IPA) and cotylenin A (CN-A). Many genes were upregulated, and only a small fraction was downregulated, upon exposure to the inducers. MJ, IPA and CN-A, but not ATRA or VD3, immediately induced the expression of mRNA for the calcium-binding protein S100P. The gene expression profile induced by MJ resembled that induced by IPA, suggesting that these inducers share many common signal transduction systems for inducing the differentiation of leukemia cells. Methyl 4,5-didehydrojasmonate was about 30 times more potent than MJ and the natural form of the stereoisomer was more effective than the unnatural isomer. It significantly stimulated both the functional and morphological differentiation of leukemia cells that had been freshly isolated from patients with hematological malignancies. Jasmonate derivatives may be promising therapeutic agents for differentiation therapy of leukemia.
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References
Weber H . Fatty acid-derived signals in plants. Trends Plant Sci 2002; 7: 217–224.
Turner JG, Ellis C, Devoto A . The jasmonate signal pathway. Plant Cell 2002; 14: S153–S164.
Katsir L, Schilmiller AL, Staswick PE, He SY, Howe GA . COI1 is a critical component of a receptor for jasmonate and the bacterial virulence factor coronatine. Proc Natl Acad Sci USA 2008; 105: 7100–7105.
Fingrut O, Flescher E . Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells. Leukemia 2002; 16: 608–616.
Ishii Y, Kiyota H, Honma Y . Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones. Leukemia 2004; 18: 1413–1419.
Flescher E . Jasmonates in cancer therapy. Cancer Lett 2007; 245: 1–10.
Collins SJ, Bonder A, Ting R, Gallo RC . Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL-60) by compounds which induce differentiation of murine leukemia cells. Int J Cancer 1980; 25: 213–218.
Honma Y . Cotylenin A—a plant growth regulator as a differentiation-inducing agent against myeloid leukemia. Leuk Lymph 2002; 43: 1169–1178.
Ishii Y, Kasukabe T, Honma Y . Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta 2005; 1745: 156–165.
Huan M, Ye Y, Chen S, Chai J, Lu J, Lin Z et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72: 567–572.
Degos L, Chomienne C, Daniel MT, Berger R, Dombret H, Fenaux P et al. Treatment of first relapse in acute promyelocytic leukaemia with all-trans retinoic acid. Lancet 1990; 336: 1440–1441.
Ohno R, Naoe T, Hirano M, Kobayashi M, Hirai H, Tubaki K et al. Treatment of myelodysplastic syndromes with all-trans retinoic acid. Blood 1993; 81: 1152–1154.
Koeffler HP . Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications. Blood 1983; 62: 709–721.
Yamada K, Honma Y, Asahi K, Sassa T, Hino K, Tomoyasu S . Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator. Br J Haematol 2001; 114: 814–821.
Kiyota H, Yoneta Y, Oritani T . Synthesis and biological activities of methyl 3,7- and 4,5-didehydrojasmonates. Phytochemistry 1997; 46: 983–986.
Kiyota H, Koike T, Higashi E, Oritani T . Syntheses and odur descriptions of cyclopropanated compounds 2. Analogues of methyl jasmonate. Flavour Fragr J 2002; 17: 267–271.
Kiyota H, Takigawa S, Kuwahara S . Syntheses and odor descriptions of cyclopropanated compounds 5. Analogues of methyl jasmonate to fix the relative stereochemistry of the two side chains. Helv Chim Acta 2004; 87: 1854–1859.
Asamitsu Y, Nakamura Y, Ueda M, Kuwahara S, Kiyota H . Synthesis and odor description of both enantiomers of methyl 4,5-didehydrojasmonate, a component of jasmin absolute. Chem Biodivers 2006; 3: 654–659.
Ishii Y, Hori Y, Sakai S, Honma Y . Control of differentiation and apoptosis of human myeloid leukemia cells by cytokinins and cytokinin ribosides, plant redifferentiation-inducing hormones. Cell Growth Differ 2002; 13: 19–26.
Ishii Y, Kasukabe T, Honma Y . Induction of CCCAAT/enhancer binding protein-d by cytokinins, but not by retinoic acid, during granulocytic differentiation of human myeloid leukaemia cells. Br J Haematol 2005; 128: 540–547.
Goldin N, Arzoine L, Heyfets A, Israelson A, Zaslavsky Z, Bravman T et al. Methyl jasmonate binds to and detaches mitochondria-bound hexokinase. Oncogene 2008; 27: 4636–4643.
Rotem R, Heyfets A, Fingrut O, Blickstein D, Shaklai M, Flescher E . Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Res 2005; 65: 1984–1993.
Reischer D, Heyfets A, Shimony S, Nordenberg J, Kashman Y, Flescher E . Effects of natural and novel synthetic jasmonates in experimental metastatic melanoma. Br J Pharmacol 2007; 150: 738–749.
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Tsumura, H., Akimoto, M., Kiyota, H. et al. Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture. Leukemia 23, 753–760 (2009). https://doi.org/10.1038/leu.2008.347
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DOI: https://doi.org/10.1038/leu.2008.347