Effects of N-acetyl-L-cysteine on adhesive strength between breast cancer cell and extracellular matrix proteins after ionizing radiation

Aims: To evaluate the effect of N-acetyl-L-cysteine (LNAC), a common ROS scavenger, on the adhesive affinity between MDA-MB-231 breast cancer cells and extracellular matrix (ECM) proteins after IR Main methods: Using static cell adhesion assays to determine the effect of various times and duration of LNAC (10 mM) treatment on IR (20 Gy)-altered adhesive affinity between MDA-MB-231 breast cancer cells and ECM, especially fibronectin; using fluorescence dye carboxy- 2,7-dichlorodihydrofluorescein diacetate to determine intracellular levels of ROS; using flow cytometry to determine cell surface integrin beta 1; and using Western blot analysis to determine vimentin expression. Key findings: Our results indicated that continuously treating the breast cancer cells with LNAC for 24 h, starting immediately after IR, could inhibit IR-induced cell adhesion to ECM proteins at 24 h post-IR. The reduction of cell adhesive affinity was correlated with a down-regulation of IR-induced ROS production and surface expression of activated integrin beta 1. When the cells were pretreated for 1 h, the inhibitory effects of LNAC were found to be either reduced or completely abrogated followed by 24 h or 2 h treatments, respectively. In addition to cell adhesion, treatment with LNAC inhibited IR-induced expression of vimentin, an epithelial-mesenchymal transition marker (EMT). Significance: The benefits of administering antioxidants during radiation therapy have been the subject of much controversy. Our,results suggest that if antioxidant treatment is to be combined with IR therapy, time of administration and treatment duration are important variables to consider. Published by Elsevier Inc.