Apoptosis in human tumor cells following treatment with p120 antisense oligodeoxynucleotide ISIS 3466.
Previously, we reported that treatment of LOX cells in vitro with phosphorothioate oligonucleotide ISIS 3466 (antisense to the human nucleolar protein p120-FB2) produced a 70% cell kill and morphological changes including nucleolar unravelling, chromatin condensation and fragmentation, and a reduction in mitotic figures consistent with apoptosis. This report shows that HeLa cells treated with ISIS 3466 also developed apoptosis: nucleosomal ladders were found when the DNA from the treated HeLa cells was extracted and run on agarose gels. The morphological changes consistent with apoptosis were found more frequently in the floating cells than in the attached cells. The percentages of floating cells and attached cells were indicators of the toxicity of the different oligonucleotides studied. Of these, oligonucleotide ISIS 3466 produced the highest percent of floating cells (78.4%). Treatment of HeLa cells with other oligonucleotides produced fewer floating cells, and the characteristic nucleosomal ladder was not found following DNA extraction.
Busch
R K
RK
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Perlaky
L
L
Valdez
B C
BC
Henning
D
D
Busch
H
H
D017209:Apoptosis; D001483:Base Sequence; D006131:Growth Inhibitors / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D006131:Growth Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C085418:ISIS 3466