SUPPRESSION OF C-MYC ONCOGENE EXPRESSION BY A POLYAMINE-COMPLEXED TRIPLEX FORMING OLIGONUCLEOTIDE IN MCF-7 BREAST-CANCER CELLS

Polyamines are excellent stabilizers of tripler DNA. Recent studies in our laboratory revealed a remarkable structural specificity of polyamines in the induction and stabilization of tripler DNA, 1,3-Diaminopropane (DAP) showed optimum efficacy amongst a series of synthetic diamines in stabilizing tripler DNA, To utilize the potential of this finding in developing an anti-gene strategy for breast cancer, we treated MCF-7 cells with a 37mer oligonucleotide to form tripler DNA in the up-stream regulatory region of the c-myc oncogene in the presence of DAP, As individual agents, the oligonucleotide and DAP did not downregulate c-myc mRNA in the presence of estradiol, Complexation of the oligonucleotide with 2 mM DAP reduced c-myc mRNA signal by 65% at 10 mu M oligonucleotide concentration, In contrast, a control oligonucleotide had no significant effect on c-myc mRNA, The expression of c-fos oncogene was not significantly altered by the tripler forming oligonucleotide (TFO), DAP was internalized within 1 h of treatment; however, it had no significant effect on the level of natural polyamines, These data indicate that selective utilization of synthetic polyamines and TFOs might be an important strategy to develop anti-gene-based therapeutic modalities for breast cancer.