Farshid Saadat, Mohammad Reza Khorramizadeh, Abbas Mirshafiey
Med Sci Monit 2005; 11(7): BR253-257
Background: Background: There is now accumulating evidence that matrixmetalloproteinases and apoptosis may play an important role in inflammation processes. This study wasundertaken to determine the effect of dexamethasone on apoptosis and matrix metalloproteinase 2 (MMP-2)activity compared with two nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and diclofenac. Material/Methods:A fibrosarcoma (WEHI-164) cell line was used for evaluating tolerability, MMP-2 activity, and apoptosis.Dexamethasone, piroxicam, and diclofenac were used at concentrations of 10-200 microg/ml in triplicate,two-fold dilutions. MMP-2 activity was assessed using zymography. For assessment of apoptosis, terminaldeoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used. Results: Cytotoxicityanalysis of dexamethasone showed a greater tolerability than diclofenac at concentrations of 10-100 microg/ml,whereas the cytotoxic effect of dexamethasone and piroxicam were parallel at doses of 5-80 microg/ml.The dose-dependent inhibitory effect of dexamethasone on MMP-2 activity was significantly less than thatof the tested NSAIDs at concentrations of 10-80 microg/ml, while it increased at doses of >100 microg/mlcompared with piroxicam. Moreover, the rate of apoptosis for dexamethasone-treated cells was 20.92%,the values for diclofenac and piroxicam being 78% and 28.15%, respectively. Conclusions: Our findingssuggest that dexamethasone is able to induce apoptosis and suppress MMP-2 activity. Collectively, dexamethasonemight be assumed as an agent which could be recommended for chemopreventive purposes.
Keywords: Dexamethasone - pharmacology, Diclofenac - pharmacology, Matrix Metalloproteinase 2 - antagonists & inhibitors, Piroxicam - pharmacology, Anti-Inflammatory Agents, Non-Steroidal - pharmacology, Antineoplastic Agents - pharmacology, Apoptosis - drug effects, Cell Line, Tumor, Cell Survival - drug effects, Dexamethasone - pharmacology, Diclofenac - pharmacology, Fibrosarcoma, Humans, In Situ Nick-End Labeling, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase Inhibitors, Piroxicam - pharmacology