Contiguous four-guanosine sequence in c-myc antisense phosphorothioate oligonucleotides inhibits cell growth on human lung cancer cells: possible involvement of cell adhesion inhibition.
A contiguous four-guanosine (4G) sequence in c-myc antisense phosphorothioate oligonucleotides caused an antiproliferative effect in smooth muscle cells. To investigate the antiproliferative effect of c-myc antisense oligonucleotides on human lung cancer cell lines, we synthesized oligonucleotides of various lengths and sequences, focusing on the contiguous four-guanosine (4G) sequence. While a c-myc antisense oligonucleotide (20AS1 (4G)) targeted to the translation initiation codon of c-myc mRNA inhibited cell growth of A549 cells by 69% at 10 microM, a scrambled oligonucleotide (20SCR1 (4G)) containing the contiguous four-guanosine (4G) sequence also inhibited cell growth by 72% at the same dose. Although treatment with either 20AS1 (4G) or 20SCR1 (4G) inhibited cell adhesion by 70% at 10 microM, expression of c-myc protein was significantly suppressed only by 20AS1 (4G) (62%), and was only weakly inhibited by 20SCR1 (4G) (32%). Furthermore, a small cell lung carcinoma cell line, Lu65, which can grow in suspension form, was highly resistant to 20AS1 (4G) treatment (IC50>20 microM). These results suggest that the cell growth inhibition by c-myc antisense oligonucleotides containing the contiguous four-guanosine (4G) sequence was possibly correlated with inhibition of cell adhesion, but not with inhibition of c-myc protein expression, via a sequence-specific non-antisense mechanism.
Saijo
Y
Y
Department of Respiratory Oncology and Molecular Medicine, Tohoku University, Aoba-ku, Sendai.
Uchiyama
B
B
Abe
T
T
Satoh
K
K
Nukiwa
T
T
D001483:Base Sequence; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D016259:Genes, myc / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D013873:Thionucleotides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013873:Thionucleotides