Role of E3330 on the migration/invasion of human breast cancer cells

The human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional DNA repair enzyme with relevant redox signalling functions. In this paper entitled “The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel”, the quinone derivative E3330, a redox inhibitor of APE1, decreased the colony formation and chemoinvasion of docetaxel-treated MDA-MB-231 cells. In addition, E3330 as single agent significantly reduced the collective cell migration. Overall, these results suggest APE1 redox function as a potential target for the modulation of cell migration and invasion in metastatic breast cancer.

Authors and Affiliations:

Patrícia S. Guerreiro¹, Eduardo Corvacho¹, João G. Costa^2,1, Nuno Saraiva², Ana Sofia Fernandes^2,1, Matilde Castro¹, Joana P. Miranda¹, Nuno G. Oliveira¹

¹Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal

²CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisbon, Portugal

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.

Journal: Chemical Biology & Drug Design

Link: http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12979/epdf