Chemoprevention by pyrimethamine |
| |
Authors: | Saadat Farshid Khorramizadeh Mohammad Reza Mirshafiey Abbas |
| |
Affiliation: | a Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran |
| |
Abstract: | 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 µg/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 µg/ml. The dose-dependent inhibitory effect of pyrimethamine on MMP-2 activity was significantly less than that of methotrexate at concentrations of 1-8 µg/ml. Moreover, the rate of apoptosis for pyrimethamine-treated cells at different doses (0.1, 1, and 10 µg/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. |
| |
Keywords: | Apoptosis Cancer Matrix metalloproteinases Pyrimethamine |
本文献已被 InformaWorld PubMed 等数据库收录! |
|