Docosahexaenoic acid-containing phosphatidylethanolamine enhances HL-60 cell differentiation by regulation of c-jun and c-myc expression.
18:1/docosahexaenoic acid (DHA)-containing phosphatidylethanolamine (PE) enhanced cell differentiation and growth inhibition of HL-60 induced by dibutyryl cAMP (dbcAMP) in a dose-dependent manner. The combined treatment of 200 microM dbcAMP and 50 microM 18:1/DHA-PE increased the NBT reducing activity, which is as an indicator of cell differentiation, to more than 75% from 40% of cells treated with 200 microM dbcAMP alone. In HL-60 cells treated with 50 microM 18:1/DHA-PE and 200 microM dbcAMP for 24 h, the expression level of c-jun mRNA and c-Jun protein were remarkably elevated compared to cells treated with dbcAMP alone. In contrast, there was no difference in the expression levels of c-fos mRNA and c-Fos protein between the combination of 18:1/DHA-PE + dbcAMP or dbcAMP alone. On the other hand, the combine treatment of 18:1/DHA-PE and dbcAMP markedly reduced the expression level of c-myc oncogene during 48 h incubation. The decreases of c-myc mRNA by 18:1/DHA-PE and/or dbcAMP was correlated with growth inhibition effect. Thus, 18:1/DHA-PE might enhance dbcAMP-induced HL-60 cell differentiation and growth inhibition by regulation of c-jun and c-myc mRNA and their products.
Ishigamori
Hideki
H
Graduate School of Fisheries Sciences, Hokkaido University, Hokkaido, Japan.
Hosokawa
Masashi
M
Kohno
Hiroyuki
H
Tanaka
Takuji
T
Miyashita
Kazuo
K
Takahashi
Koretaro
K
D003994:Bucladesine / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects / Q000502:physiology*; D016259:Genes, myc / Q000187:drug effects / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D009580:Nitroblue Tetrazolium / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D010714:Phosphatidylethanolamines; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D009580:Nitroblue Tetrazolium; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases