Daily addition of an anti-c-myc DNA oligomer induces granulocytic differentiation of human promyelocytic leukemia HL-60 cells in both serum-containing and serum-free media.
Expression of the human protooncogene c-myc is necessary for replication, and may be inhibited in a sequence-specific, dose-dependent manner by an antisense oligodeoxynucleotide specific for the first five codons of c-myc mRNA. Antisense inhibition of c-myc inhibits the proliferation and enhances the differentiation of the HL-60 human promyelocytic leukemia cell line. In order to raise the efficacy of antisense oligomers, HL-60 cells were grown in a serum-free medium so as to minimize nuclease activity in the culture medium. Daily addition of anti-c-myc oligomer was then found to induce terminal granulocytic differentiation of 80% or more of HL-60 cells, and inhibit colony formation by greater than 50%, comparable to 1% Me2SO.
Bacon
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Department of Chemistry, University of South Florida, Tampa 33620.
Wickstrom
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D001769:Blood; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000502:physiology*; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003470:Culture Media; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide