Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress proliferation and induce apoptosis of differentiated HL-60 human leukemia cell.
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, gamma-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)microM 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.
Jung
K C
KC
Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
Park
C H
CH
Hwang
Y H
YH
Rhee
H S
HS
Lee
J H
JH
Kim
H K
HK
Yang
C H
CH
D017209:Apoptosis / Q000187:drug effects*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D019281:Dimerization; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005227:Fatty Acids; C499330:MAX protein, human; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D004247:DNA; D004121:Dimethyl Sulfoxide