Abbas Mirshafiey, Mohammad Reza Khorramizadeh, Farshid Saadat, Bernd H.A. Rehm
Med Sci Monit 2004; 10(10): PI105-109
Background:An emerging body of literature has recently defined a reduced risk of cancer following the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which are generally able to exert an apoptotic property and inhibitory effects on the activity and/or expression of matrix metalloproteinases (MMPs). This study was undertaken to explore the role of a newly designed NSAID, M2000 (C[sub]6[/sub]H[sub]10[/sub]O[sub]7[/sub]), as an anti-inflammatory drug in chemoprevention therapy under in vitro conditions.Material/Methods: The influence of M2000 on a fibrosarcoma cell line (WEHI-164) was investigated using an in vitro cytotoxicity assay, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay to assess apoptosis, and gelatin zymography for evaluating the activity of matrix metalloproteinase 2 (MMP-2).Results: Cytotoxicity analysis of M2000 showed a much higher tolerability than the other tested drugs (diclofenac, piroxicam, and dexamethasone) in that it showed no cytotoxic effect compared with them. The dose-dependent inhibitory effect of M2000 at concentrations of 20, 40, 80, and 200 µg/ml was significantly greater than that of dexamethasone and of piroxicam at a concentration of 200 µg/ml, whereas the inhibitory activity of M2000 paralleled diclofenac at doses of 10, 20, 40, and 200 µg/ml. Moreover, the apoptotic efficacy of M2000 was similar to that of dexamethasone.Conclusions: Based on our data, the induction of apoptosis together with MMP-2 inhibition could be indicative of a chemopreventive property of M2000. Thus this novel NSAID might be considered as a chemopreventive drug in the potential prevention and treatment of cancer and in inhibition of the angiopathogenic process.
Keywords: Animals, Anti-Inflammatory Agents - pharmacology, Antineoplastic Agents - pharmacology, Apoptosis - drug effects, Cell Line, Tumor, Fibrosarcoma - enzymology, Fibrosarcoma - pathology, Fibrosarcoma - prevention & control, Hydrocarbons - pharmacology, Matrix Metalloproteinase 2 - metabolism, Mice, Mice, Animals, Anti-Inflammatory Agents - pharmacology, Antineoplastic Agents - pharmacology, Apoptosis - drug effects, Cell Line, Tumor, Fibrosarcoma - prevention & control, Hydrocarbons - pharmacology, Matrix Metalloproteinase 2 - metabolism, Mice