Chemoprevention by pyrimethamine.
The goal of the current research was to investigate the chemopreventive potency of an antimalaria drug, pyrimethamine, in in vitro conditions. The fibrosarcoma (WEHI-164) cell line was used for evaluating cytotoxicity, matrix metalloproteinase 2 (MMP-2) activity, and apoptosis. Pyrimethamine and methotrexate were used at concentrations of 0-8 microg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymoanalysis method. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. Cytotoxicity analysis of pyrimethamine showed a greater tolerability than methotrexate at concentrations of 1-8 microg/ml. The dose-dependent inhibitory effect of pyrimethamine on MMP-2 activity was significantly less than that of methotrexate at concentrations of 1-8 microg/ml. Moreover, the rate of apoptosis for pyrimethamine-treated cells at different doses (0.1, 1, and 10 microg/ml) was 3.30%, 9.42%, and 11.32%, respectively. Our data suggest that pyrimethamine enables suppression of MMP-2 activity and induces apoptosis that could be assumed for chemoprevention therapy.
Saadat
Farshid
F
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Khorramizadeh
Mohammad Reza
MR
Mirshafiey
Abbas
A
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D008727:Methotrexate / Q000494:pharmacology; D011739:Pyrimethamine / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2; D008727:Methotrexate; D011739:Pyrimethamine