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

• Published in: Life sciences (1973) Vol. 93; no. 21; pp. 798 - 803
• Main Authors: Cheng, Huiwen, Lee, Shin Hee, Wu, Shiyong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 13.11.2013
• Subjects: acetylcysteine; Acetylcysteine - administration & dosage; Acetylcysteine - pharmacology; antioxidants; Breast cancer; breast neoplasms; Breast Neoplasms - pathology; Catalase - pharmacology; CD29 antigen; Cell adhesion; Cell Adhesion - drug effects; Cell Adhesion - radiation effects; Down-Regulation - drug effects; Drug Administration Schedule; extracellular matrix; Extracellular Matrix Proteins - metabolism; fibronectins; flow cytometry; fluorescence; Free Radical Scavengers - administration & dosage; Free Radical Scavengers - pharmacology; Humans; Integrin; Integrin beta1 - metabolism; Ionizing radiation; LNAC; neoplasm cells; Radiation, Ionizing; radiotherapy; Reactive Oxygen Species - metabolism; Tumor Cells, Cultured; vimentin; Vimentin - metabolism; Western blotting; Ionizing radiation; Breast cancer; Integrin; LNAC; Cell adhesion
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2013.09.029

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 (10mM) treatment on IR (20Gy)-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 β1; and using Western blot analysis to determine vimentin expression. Key findings: Our results indicated that continuously treating the breast cancer cells with LNAC for 24h, starting immediately after IR, could inhibit IR-induced cell adhesion to ECM proteins at 24h 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 β1. When the cells were pretreated for 1h, the inhibitory effects of LNAC were found to be either reduced or completely abrogated followed by 24h or 2h 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.