Anti-sense phosphorothioate oligonucleotides have both specific and non-specific effects on cells containing human papillomavirus type 16.
A range of specific nuclease resistant phosphorothioate oligodeoxynucleotides (S-oligos) complementary to mRNA of human papillomavirus type 16 (HPV16), were tested for their ability to inhibit cell proliferation and to alter the level of HPV-specific mRNA and proteins in CaSki cells, a human cervical carcinoma cell line containing HPV16 DNA. Only certain of the S-oligos to the viral upstream regulatory region (URR) and the early viral open reading frames (ORF), E6 and E7, were found to display any activity on the cells. These S-oligos were found to exhibit potent anti-proliferative activity at concentrations between 0.25 microM and 20 microM, inhibiting the uptake of [3H]-thymidine into CaSki cells by up to 90% at higher concentrations. The rate of synthesis of E6 and E7 proteins and the steady state level of the E7 protein however remained largely unchanged. E7 protein exhibited a greater decrease in phosphorylation in the presence of only one of the antisense oligos. Other S-oligos including a random sequence, unmodified sequences or O-methylphosphonate modified oligos, had no specific effect on the cells. The results imply that the anti-sense S-oligonucleotides had both specific anti-HPV16 and other non-specific effects on cell proliferation and synthesis of virally encoded proteins.
Storey
A
A
International Center for Genetic Engineering and Biotechnology, Trieste, Italy.
Oates
D
D
Banks
L
L
Crawford
L
L
Crook
T
T
D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D016366:Open Reading Frames / Q000187:drug effects; D027383:Papillomaviridae / Q000187:drug effects*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D012367:RNA, Viral / Q000187:drug effects; D012097:Repressor Proteins; D013873:Thionucleotides / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
C068651:E6 protein, Human papillomavirus type 16; D016376:Oligonucleotides, Antisense; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; D013873:Thionucleotides; C059731:oncogene protein E7, Human papillomavirus type 16