Enhancement of non-homologous end joining DNA repair capacity confers cancer cells resistance to the novel selenophene compound, D-501036

Cancer Lett. 2011 Oct 1;309(1):110-8. doi: 10.1016/j.canlet.2011.05.023.

Abstract

D-501036 is a promising anti-cancer compound that exhibits potent anti-proliferative activity against various types of human cancers through the induction of double strand DNA breaks. To determine drug resistance mechanism related to this class of DNA-damaging agents, a KB-derived D-501036-resistant cell line (S4) was established. Results showed that S4 cells exhibit enhanced DNA rejoining ability as compare to KB cells, through up-regulation of the non-homologous end joining activity. In conclusion, enhancement of NHEJ activity plays important role in the development of D-501036-resistance and targeting NHEJ-related molecules maybe able to overcome drug resistance to DNA damaging agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics*
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Humans
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / therapeutic use
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Up-Regulation
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • 2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrole
  • Antineoplastic Agents
  • Organoselenium Compounds
  • Pyrroles