729: Nupharidine inhibits NF-kappa B activity, has synergistic cytotoxic activity with cisplatin and etoposide and induces apoptosis Academic Article uri icon

abstract

  • Background: Pro-survival AKT-phosphorylation at serine 473 has been shown by us to be mediated by DNA-PKcs, a core component of the non-homologous end joining (NHEJ) pathway, in response to DNA damaging chemotherapy. This occurs preferentially in clinically chemo-resistant cells. Importantly, we have also shown that DNA-PKcs or AKT inhibition restores platinum sensitivity in vitro and in vivo (Stronach, 2011). Here we assess the broader extent of involvement of DNA-PKcs and other NHEJ proteins in response to cisplatin and gemcitabine using poor prognosis pancreatic and ovarian cancer models. Additionally, we investigate interactions between the NHEJ and homologous recombination (HR) pathways following DNA-PKcs inhibition. Materials and Methods: Cell viability and apoptosis were assessed by MTT analysis and measurement of caspase 3/7 activity …

publication date

  • January 1, 2014