Inhibition of leukaemia cell proliferation by folic acid-polylysine-mediated introduction of c-myb antisense oligodeoxynucleotides into HL-60 cells.
The inhibitory effect of c-myb antisense oligodeoxynucleotides (ODNs) conjugated to folic acid (FA) on HL-60 cell proliferation was examined. Folic acid was covalently linked to a polylysine chain and purified by gel chromatography. Sterile FA-polylysine was complexed with c-myb sense and antisense. Exposure of HL-60 cells to the FA-polylysine-c-myb antisense ODN complex resulted in a down-regulation of c-myb expression and a greater inhibition of proliferation than that obtained using free ODNs. Moreover, FA-polylysine conjugate alone or complexed to c-myb sense ODN was not toxic to cells. The antigenic properties and uptake of the vitamin were not affected by the polylysine chain. These data suggest that this strategy is potentially useful for the selective delivery of anti-oncogene-targeted ODNs into cancer cells.
Citro
G
G
Laboratorio Chemioterapia Sperimentale, Istituto Tumori Regina Elena, Roma, Italy.
Szczylik
C
C
Ginobbi
P
P
Zupi
G
G
Calabretta
B
B
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003062:Codon; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005492:Folic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000633:toxicity*; D009857:Oncogenes; D011107:Polylysine / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D003062:Codon; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D011107:Polylysine; D005492:Folic Acid