Targeting molecular components that are critically involved in the maintenance of
genome stability is a promising approach for overcoming intrinsic
tumor cell resistance to
DNA-damaging treatments. In mammalian cells, the Ku-dependent non-homologous end-joining repair pathway is the predominant process for the repair of double-strand breaks (DSBs) in
DNA. Previously,
RNA aptamers were selected to efficiently block
DNA-binding activity of the
Ku protein in vitro. In the present study, we have tested the efficacy of
RNA aptamers against the
Ku protein as molecular sensitizer of MCF-7
breast carcinoma cells to DNA-damage. Toward this end, we established MCF-7 cell sublines stably expressing SC4 aptamer RNAs under the control of the human 7SL
small nuclear RNA gene promoter. Vector-transfected (MCF/7SL) cells and cells stably expressing SC4 aptamers (MCF/SC4) were exposed to the anticancer
drug etoposide and cellular responses to DNA-damage were evaluated. We found that the presence of
RNA aptamers against
Ku protein enhanced
etoposide-induced growth inhibition of MCF-7
breast cancer. The SC4 aptamer-mediated sensitization of MCF-7 cells to the anticancer
drug is attributable to an increased susceptibility of these cells to apoptosis. The observed effects cannot be accounted for by the differential expression levels of
Ku protein in control and SC4 aptamer-expressing cells, but are rather due to augmented
DNA binding-capacity of
Ku protein, as demonstrated in in vitro studies. Thus,
RNA aptamers against
Ku protein show potential to sensitize MCF-7
breast carcinoma cells to
DNA-damaging agents.