Suppression of telomerase activity by pyrimethamine: implication to cancer.
Although pyrimethamine (Tindurin) appears to be effective in the prevention and treatment of some infectious diseases, very little information exists on its unpredictable properties. We design this study to evaluate its anti-tumoral effect on a model of cell line.



The cytotoxic influence of Pyrimethamine on prostate cell line was investigated using an in vitro colometric assay. The potential modulatory effects on metastasis, apoptosis, and immortality characteristics of cells were assessed with gelatin zymography, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and telomeric repeat amplification protocol, respectively.



Cytotoxicity analysis of pyrimethamine revealed a dose-dependent fashion. An apoptotic influence of pyrimethamine was also confirmed by data obtained from TUNEL assay. Dose-dependent inhibitory effect on matrix metalloproteinases (MMP) was seen in pyrimethamine. A potent inhibitory effect of pyrimethamine was also established by data achieved from TRAPeze telomerase detection kit.



Collectively, as induction of apoptosis together with MMP and telomerase inhibition could be indicative of cancer treatment, pyrimethamine might be considered as a chemopreventative agent in cancer.
Khorramizadeh
Mohammad Reza
MR
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Saadat
Farshid
F
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Vaezzadeh
Farhad
F
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Safavifar
Farnaz
F
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Bashiri
Hassan
H
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Jahanshiri
Zahra
Z
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Momeny
Majid
M
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
Mirshafiey
Abbas
A
Department of Pathobiology, School of Public Health, Medical Sciences/University of Tehran, P.O. Box: 14155-6446, Tehran, Iran.
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D011739:Pyrimethamine / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D019098:Telomerase; D020778:Matrix Metalloproteinase 2; D011739:Pyrimethamine