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Published on: September 3, 2013
Effect of suramin on the mitogenic response of the human prostate carcinoma cell line PC-3
M W Ewing1, S C Liu, J R Gnarra
1Urologic Oncology Section, Surgery Branch, NCI, National Institutes on Health, Bethesda, MD 20892.
Background:
Suramin is an anthelmintic drug that recently has been shown to have clinical efficacy in the treatment of patients with some advanced malignancies, including prostate carcinoma. The current study was done to assess the effect of suramin at clinically relevant doses on the growth in culture of a human prostatic carcinoma cell line, PC-3.
Methods:
The antiproliferative effect of varying doses of suramin on PC-3 was assessed. Northern blot analysis was done to assess the potential changes in genetic expression at different times after the initiation of treatment.
Results:
Suramin inhibited the proliferation of PC-3 in a dose-related manner (concentration range, 30-300 microM). Compared with fetal calf serum 2%, when the cells were grown in fetal calf serum 10%, higher concentrations of suramin were required to inhibit tritiated thymidine incorporation. When grown in RPMI without supplement, the PC-3 cell number remained the same. When 100 microM suramin was included, the cell number decreased. By contrast, when RPMI was supplemented with insulin, transferrin, and selenium (ITS), PC-3 grew well. The inhibition of the proliferation of PC-3 cells by suramin was decreased when ITS were added to the cells grown under serum-free conditions.
Conclusions:
These results were consistent with the hypothesis that in vitro inhibition of the growth of PC-3 cells by suramin may be caused, at least in part, by the growth factor antagonism of the drug. In fetal calf serum 2%, the suramin inhibition was reversible after 3 days. If the treatment was extended to 6 days, however, the PC-3 cells were unable to recover. Cell-cycle analysis revealed that, after 6 days of treatment, there was a decrease in the number of cells in G1 that corresponded with an increased number of cells in G2/M. This suggested that critical antineoplastic events were occurring during this time. Molecular analysis did not detect any altered expression of actin, transforming growth factors alpha or beta, or histone compared with untreated control samples.
Insights
Suramin, an anthelmintic drug, effectively inhibits prostate cancer cell (PC-3) growth in vitro. This effect is linked to growth factor antagonism and leads to cell cycle arrest, suggesting potential anticancer applications.
Area of Science:
- Oncology
- Pharmacology
Background:
- Suramin is an anthelmintic drug with demonstrated efficacy in advanced malignancies.
- Its potential in treating prostate carcinoma warrants further investigation.
Purpose of the Study:
- To assess the in vitro effect of suramin on human prostate carcinoma (PC-3) cell growth.
- To investigate the impact of suramin on PC-3 cell genetic expression.
Main Methods:
- PC-3 cells were treated with varying doses of suramin.
- Antiproliferative effects were measured by tritiated thymidine incorporation.
- Northern blot analysis assessed changes in genetic expression.
Main Results:
- Suramin inhibited PC-3 cell proliferation in a dose-dependent manner.
- Inhibition was influenced by culture medium supplements like fetal calf serum and ITS.
- Prolonged suramin treatment (6 days) led to irreversible inhibition and cell cycle arrest in G2/M phase.
Conclusions:
- In vitro inhibition of PC-3 cell growth by suramin is likely mediated by growth factor antagonism.
- Suramin induces critical antineoplastic events, including cell cycle arrest.
- Molecular analysis did not reveal significant changes in the expression of tested genes.
