DJ-1 Protects Breast Cancer Cells Against 2'-Benzoyloxycinnamaldehyde-induced Oxidative Stress Independent of Nrf2.

2'-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent. BCA effectively inhibited proliferation of MDA-MB-435 more than in MCF-7 breast cancer cells. Our recent findings showed that DJ-1 protects MCF7 cells from BCA-induced oxidative stress via its mitochondrial translocation and inhibition of the mitochondrial perturbation (Ismail et al., 2012). In this study, we addressed the question of whether Nrf2 works downstream to DJ-1 in mediating differential antiproliferation effects in MCF-7 and MDAMB-435 breast cancer cells induced by BCA treatment. BCA upregulated the expression and induced nuclear translocalization of DJ-1 and Nrf2 in only MCF-7 cells. However, in MDA-MB-435, BCA increased only Nrf2 expression without inducing DJ-1 and/or Nrf2 protein translocalization to the nucleus. Furthermore, DJ-1 knockdown decreased DJ-1 expression in both cells without affecting Nrf2 and its downstream target γ-GCS, suggesting that DJ-1-induced cell protection and works independent of Nrf2 signaling pathway.