Investigating the mechanism of novel anticancer agent, AS1411 : does metabolism to guanine play a role?

AS1411 is an oligonucleotide that has shown promising results in lab experiments and clinical trials as an anti-cancer drug, Likewise, treatments with guanine based purine compounds (GBPCs) have demonstrated similar anti-proliferative effects in vitro. This activity is dependent on the HGPRT enzyme. Similarities in activity and physical structure has led us to believe that AS1411 and GBPCs operate by a similar mechanism. To test this, we compare the activity of both in the presence of HGPRT siRNAs and HGPRT deficient cells. While siRNA treatment was unable to alter the activity of GBPCs or AS1411 in our cell lines, HGPRT deficient cells did exhibit statistically significant differences in relative proliferation when treated with both AS1411 and GBPCs. While inconclusive, these results suggest that HGPRT is implicated in the activity of both compounds