Matrix metalloproteinase activity in transformed cells exposed to an antioxidant

Abstract

We showed that antioxidant N-acetylcysteine (NAC, 2–10 mM) rapidly (in 2 h) and completely deactivated the activity of matrix metalloproteinases (MMPs) (MMP-2 and MMP-9 gelatinases and MMP-1 and MMP-8 collagenases) secreted by transformed 3T3-SV40 mouse fibroblasts into the medium. The same MMP inhibition took place in the cell-free medium conditioned by HT-1080 fibroblasts. This suggests that the direct chemical interaction between NAC and MMP resulted in the loss of MMP activity. In addition to this inhibitory effect, NAC decreased MMP-1 and MMP-9 (but not MMP-2) production in the cell medium. However, the level of MMP-1 and MMP-9 inhibitors (TIMP-1) remained normal, indicating a shift in the balance between the enzyme and inhibitor. The correlation between MMP-2 and the tissue enzyme inhibitor TIMP-2 level was similar in control and NAC-treated cells. Moreover, reorganization of collagen type I at the cell surface was observed. Taken together, our results suggest that NAC exposure results in extracellular matrix remodeling and a change in cellular functions.