Induction of apoptosis and mitosis inhibition by degraded DNA lipotransfection mimicking genotoxic drug effects.
Genotoxic damage induces cell cycle arrest and/or apoptosis by activation of p53 oncosuppressor protein. A number of anticancer drugs are genotoxic and their damaging effect upon cells is mediated by this mechanism. Microinjection of defined DNA species directly into nucleus has been reported previously to activate p53 and inhibit cell cycle. Here, we demonstrate that simple addition of heterogeneous degraded DNA to cultured cells (Rat-1 fibroblasts) in combination with lipotransfecting agent DOTAP leads to apoptosis induction and mitosis inhibition by a molecular mechanism which mimics that of the cellular response to genotoxic anticancer agents. Indeed, both cellular effects induced by lipotransfected degraded DNA (essentially, heterogeneous small DNA fragments) are associated to p53 activation and modulated by two apoptosis-related genes, such as bcl-2 and c-myc, which also modulate the apoptotic threshold to anticancer agents. Here we raise the hypothesis of exogenous DNA segment lipotransfection as possible new tool for anticancer therapy.
Schiavone
N
N
Department of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni 50, Florence, 50134, Italy.
Papucci
L
L
Luciani
P
P
Lapucci
A
A
Donnini
M
M
Capaccioli
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D009153:Mutagens / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D014162:Transfection / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D009153:Mutagens; D000644:Quaternary Ammonium Compounds; D016159:Tumor Suppressor Protein p53; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane