Exploiting RNA as anticancer target for synthetic polyamines

RNA component is being investigated as a potential target for new antitumor agents (Leland & Raines 2001). Current available technologies used for RNA destruction include approaches that utilize the activity of protein ribonucleases such as antisense oligonucleotide, small interfering RNA (siRNA), RNase P-associated external guide sequence, and sequence-specific approaches. Endogenous protein RNases can be utilized to target specific RNA for degradation by employing antisense oligonucleotides and double-stranded siRNA molecules together with other modern techniques which led to programmed cell death (Tafech et al. 2006). Onconase®, an amphibian endoribonuclease (RNase), is currently in stage 3 clinical trials, demonstrating inhibition of multiple forms of cancer cell growth both in vitro and in vivo (Halicka et al. 2007, Ramos-Nino et al. 2005, Lee et al. 2007), and demonstrating RNA as a validated target for cancer therapy. The aim of the present study was to verify if synthetic spermine analogue polyamines were able to interact with this validated target. Although simple in structure, the polycationic polyamines (PAs) spermidine and spermine and their diamine precursor putrescine are essential factors for growth in eukaryotic cells (Wallace 2009) and are able to interact with a wide number of biological targets (Minarini et al. 2010, Bonaiuto et al. 2012, Melchiorre et al. 2010). Experimental and modelling data demonstrated that PA and their analogues undoubtedly interact with naked DNA and affect DNA conformation and aggregation (Valasinas et al. 2003, Casero & Marton 2007, Zini et al. 2009). Recent results also showed that natural PAs are able to interact with RNA altering its integrity (Fimognari et al. 2012, Fimognari et al. 2008, Fimognari et al. 2009). Some synthetic spermine analogues were investigated about their ability to interact with RNA through the evaluation of RNA damage performed by microfluidic capillary electrophoresis (Agilent 2100 bioanalizier) (Mueller et al. 2000). The different electropherograms indicated the RNA damage caused by the investigated synthetic PAs, and a software algorithm allowed the calculation of the RNA Integrity Number (RIN) (Schroeder et al. 2006). The results of this study will be reported and discussed along with the electropherograms of each synthetic PA.