Apoptotic efficacy and inhibitory effect of dexamethasone on matrix metalloproteinase.
BACKGROUND
There is now accumulating evidence that matrix metalloproteinases and apoptosis may play an important role in inflammation processes. This study was undertaken 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.


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, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used.


RESULTS
Cytotoxicity analysis 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 that of the tested NSAIDs at concentrations of 10-80 microg/ml, while it increased at doses of >100 microg/ml compared 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 findings suggest that dexamethasone is able to induce apoptosis and suppress MMP-2 activity. Collectively, dexamethasone might be assumed as an agent which could be recommended for chemopreventive purposes.
Saadat
Farshid
F
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Khorramizadeh
Mohammad Reza
MR
Mirshafiey
Abbas
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D005354:Fibrosarcoma; D006801:Humans; D020287:In Situ Nick-End Labeling; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D010894:Piroxicam / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D010894:Piroxicam; D004008:Diclofenac; D003907:Dexamethasone; D020778:Matrix Metalloproteinase 2