Mine Erguven, Nuriye Akev, Aysegul Ozdemir, Ebru Karabulut, Ayhan Bilir
Med Sci Monit 2008; 14(8): BR165-173
The significant roles of telomerase in carcinogenesis and drug resistance have attracted growing attention as potential therapies. The aim of the study was to investigate the effect of suramin on the telomerase activity of C6 glioma cells and on the growth of C6 glioma spheroids.
Material and Method: C6 rat glioma cells were treated with suramin at doses of 175 and 250 microM, and also with an increasing dosage for 96 hours. The effect of suramin on monolayer and spheroid cultures was determined by evaluating cell proliferation, spheroid growth, bromodeoxyuridine labeling index, changes of spheroid ultrastructure, and telomerase activity.
Results: Suramin inhibited telomerase activity in a dose-dependent manner. Suramin at 250 microM and 175 microM reduced telomerase activity and cell proliferation, spheroid growth, and bromodeoxyuridine labeling index. These groups commonly revealed distorted nuclei (i.e., nucleolus segregation at 250 microM, many vacuoles, vacuole fusions, and smoothing of the cell surface). Contrary to the effects of individually applied suramin, the increased dose of suramin increased telomerase activity but inhibited cell proliferation and bromodeoxyuridine labeling index only at the 24th and 96th hours; it inhibited spheroid growth at the 96th hour. The increased dose of the suramin-treated group showed changes of spheroid ultrastructure similar to those of the control group except for rarely observed vacuoles or vacuole fusion and microvilli.
Conclusions: To the best of our knowledge, this is the first study in the English language to show in vitro cytotoxic effect of suramin via telomerase inhibition on C6 glioma cells and spheroids.
Keywords: Telomerase - antagonists & inhibitors, Suramin - pharmacology, Rats, Spheroids, Cellular - ultrastructure, Glioma - pathology, DNA, Neoplasm - biosynthesis, Cell Nucleolus - ultrastructure, Cell Proliferation - drug effects, Tumor Cells, Cultured, Time Factors, Cell Cycle - drug effects, Bromodeoxyuridine - metabolism, Animals