Non-small cell lung cancer is susceptible to induction of DNA damage responses and inhibition of angiogenesis by telomere overhang oligonucleotides

Abstract

Exposure of the telomere overhang acts as a DNA damage signal, and exogenous administration of an 11-base oligonucleotide homologous to the 3′-telomere overhang sequence (T-oligo) mimics the effects of overhang exposure by inducing senescence and cell death in non-small cell lung cancer (NSCLC) cells, but not in normal bronchial epithelial cells. T-oligo-induced decrease in cellular proliferation in NSCLC is likely directed through both p53 and its homolog, p73, with subsequent induction of senescence and expression of senescence-associated proteins, p21, p33ING, and p27Kip1 both in vivo and in vitro. Additionally, T-oligo decreases tumor size and inhibits angiogenesis through decreased VEGF signaling and increased TSP-1 expression.