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Differentiation

Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress proliferation and induce apoptosis of differentiated HL-60 human leukemia cell

Leukemia volume 20, pages 122–127 (2006)Cite this article

Abstract

c-Myc is instrumental in the progression of Burkitt's lymphoma including HL-60 human leukemia cells. We tested fatty acids for their inhibitory effect on the DNA binding of c-Myc/Max dimeric proteins of human origin, prepared as recombinant proteins encompassing DNA binding (basic) and dimerization (HLHZip) domain, and found that those suppress proliferation and induce apoptosis of DMSO-differentiated HL-60 cells. The analyzed IC50 values of myristic acid, stearic acid, γ-linolenic acid, linoleic acid, linolenic acid and arachidonic acid by EMSA were 97(±3), 2.2(±1.2), 55(±5), 32(±2), 62(±12), 22(±2) μ M for DNA binding of recombinant c-Myc/Max, respectively. According to the results shown by XTT assay, their influence on proliferation was quite different from the rank order of IC50. Whereas the degree of influence of the unsaturated fatty acids on the proliferation of DMSO-differentiated HL-60 cells was similar, the influence of saturated fatty acids, stearic acid in particular, was very weak at same concentrations. In addition, we confirmed that these fatty acids have no influence on the expression of c-Myc in DMSO-differentiated HL-60 cells. Our experiments demonstrated that the inhibitors for the DNA binding of c-Myc/Max contribute to the downregulation of Myc-dependent proliferation and to the inducement of apoptosis, and serve as an exploration of potent new inhibitors.

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Acknowledgements

Financial support in part from the Brain Korea 21 program is gratefully acknowledged. We thank the Ministry of Education for the Brain Korea 21 fellowship.

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  1. Department of Chemistry, Seoul National University, Seoul, Republic of Korea

    K C Jung, C H Park, Y H Hwang, H S Rhee, J H Lee, H-K Kim & C H Yang

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  1. K C Jung
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Correspondence to C H Yang.

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Jung, K., Park, C., Hwang, Y. et al. Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress proliferation and induce apoptosis of differentiated HL-60 human leukemia cell. Leukemia 20, 122–127 (2006). https://doi.org/10.1038/sj.leu.2404022

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