title: Phosphodiester oligonucleotides inhibit mitosis and trigger apoptosis by a non-antisense, p53-mediated mechanism.
abstract: Oligodeoxyribonucleotides (ODNs) are currently employed to switch-off genes selectively routinely in the laboratory practice. The drawback of ODN application is that they have been often reported to elicit non-antisense effects by different mechanisms. Recently, it has been shown that double-stranded DNA oligonucleotides (30-mers) with protruding ends activate p53 in a cell-free system. In a previous work, we described that simple addition to the culture medium of heterogeneous DNA combined with cationic lipids culminated in inhibition of mitosis and induction of apoptosis. Here, we report that the same effects are achieved by lipotransfecting cultured cells with phosphorodiester ODNs (30-mers). Such effects of ODN were mediated by a non-antisense mechanism that required the wild-type form of the p53 oncosuppressor protein and was dependent on ODN concentration. Mitosis inhibition and apoptosis induction appeared to be determined by the 3' and 5' free ends of ODNs, which activated p53 independently from their sequence. Most probably, this mechanism is analogous to that evoked by genotoxic agent-induced DNA damage or by lipotransfecting cells with heterogeneous DNA.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Italy. lpapucci@yahoo.com
authors.forename: Laura
authors.initials: L
authors.lastname: Papucci
authors.forename: Nicola
authors.initials: N
authors.lastname: Schiavone
authors.forename: Martino
authors.initials: M
authors.lastname: Donnini
authors.forename: Andrea
authors.initials: A
authors.lastname: Lapucci
authors.forename: Ettore
authors.initials: E
authors.lastname: Luzi
authors.forename: Alessio
authors.initials: A
authors.lastname: Tempestini
authors.forename: Ewa
authors.initials: E
authors.lastname: Witort
authors.forename: Sergio
authors.initials: S
authors.lastname: Capaccioli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D002474:Cell-Free System; D004952:Esters; D005229:Fatty Acids, Monounsaturated; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D004952:Esters; D005229:Fatty Acids, Monounsaturated; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D000644:Quaternary Ammonium Compounds; D016159:Tumor Suppressor Protein p53; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane