Previous reports from this laboratory have shown marked cytocidal effects of the ISIS-3466 antisense phosphorothioate oligodeoxynucleotide to the human nucleolar protein p120 on human cancer cell lines in vitro and inhibition of tumor growth in vivo in an i.p/i.p. LOX cell model (L. Perlaky et al. Anti-Cancer Drug Design 8:3-14, 1993). In this study, light and fluorescence microscopy showed that the number of LOX cells in mitosis decreased by 50% after incubation for 4 h in 0.2-0.4 microM antisense oligonucleotide; a 70% reduction in cell number was found from 8-72 h post-treatment. In addition, marked unravelling of nucleolar structures and chromatin fragmentation was found after a 4-h incubation. The nucleolar unravelling occurred in varying degrees ranging from partial unfolding to almost complete separation of the strands of nucleolar residues. Twenty four hours post-treatment, immunofluorescence staining with the anti-p120 monoclonal antibody showed reduced nucleolar protein p120 and translocation of the p120 protein from the nucleoli to the nucleoplasm. Analysis of the mechanisms of the nucleolar unravelling and inhibition of mitosis will provide further understanding of the cytocidal effects of the ISIS-3466 antisense oligonucleotide.
- MeSH
- amelanotický melanom * genetika chemie patologie MeSH
- antigeny nádorové * účinky léků MeSH
- antisense oligodeoxyribonukleotidy * MeSH
- antisense oligonukleotidy farmakologie genetika MeSH
- buněčné jadérko * účinky léků MeSH
- buněčné jádro účinky léků MeSH
- chromatin účinky léků MeSH
- fluorescenční mikroskopie MeSH
- jaderné proteiny * účinky léků MeSH
- lidé MeSH
- mitóza účinky léků MeSH
- molekulární sekvence - údaje MeSH
- nádorové buňky kultivované účinky léků MeSH
- sekvence nukleotidů MeSH
- thionukleotidy farmakologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
