The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel

Chem Biol Drug Des. 2017 Oct;90(4):561-571. doi: 10.1111/cbdd.12979. Epub 2017 May 3.

Abstract

The human apurinic/apyrimidinic endonuclease 1 (APE1) is an ubiquitous multifunctional DNA repair enzyme and a redox signalling protein. Our work addressed the inhibition of APE1 redox function using E3330, as single agent or in combination with docetaxel (DTX), in human breast cancer MDA-MB-231 cells. E3330 decreased the colony formation of DTX-treated cells. In addition, E3330 alone significantly reduced the collective cell migration as assessed by the wound-healing assay, whereas the combined treatment decreased chemoinvasion. These results suggest that the inhibition of APE1 redox function might have therapeutic potential by modulating cell migration and invasion in metastatic breast cancer.

Keywords: E3330; apurinic/apyrimidinic endonuclease 1; breast cancer; cell migration and invasion; docetaxel.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Benzoquinones / pharmacology*
  • Breast / drug effects
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / antagonists & inhibitors*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
  • Docetaxel
  • Female
  • Humans
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control*
  • Oxidation-Reduction / drug effects
  • Propionates / pharmacology*
  • Taxoids / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Propionates
  • Taxoids
  • E 3330
  • Docetaxel
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase