Related Experiment Videos
The effect of schedule, protein binding and growth factors on the activity of suramin
R Lopez Lopez1, G J Peters, A C van Loenen
1Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Abstract:
Suramin has been shown to have antiproliferative activity, either by blocking the binding of growth factors to their receptors or by inhibiting critical cellular enzymes. In 6 different cell lines from 5 tumour types (MCF-7, MCF-7/ADRR, PC3, HT-29, UM-SCC-11B and SW-1573/IR500), we studied the effect of scheduling of suramin, of FCS and of human serum albumin (HSA), of epidermal growth factor (EGF) and of the addition of growth factors in serum-free medium on the activity of suramin. The concentration of suramin which gave 50% growth inhibition (IC50) varied from 45 microM in SW-1573/IR500 to 153 microM in PC3 cells grown in medium supplemented with 5% FCS, after 6 days of continuous exposure. Exposure for more than 4 days did not enhance the sensitivity to suramin, except in PC3. At exposure to suramin for 1 day followed by 5 days recovery, high IC50 values (greater than 0.5 mM) were observed in MCF-7 cells. In medium with 1% and 0.5% FCS these values were 3 to 8 and 14 to 26 times lower respectively. Addition of HSA increased the IC50 in PC3 and MCF-7 cells. Suramin binding to protein was dependent on the concentration of protein and of suramin. Excess of EGF in medium with different FCS concentrations did not change the IC50 values of suramin in PC3 and MCF-7 cells. Addition of EGF, fibroblast growth factor or platelet-derived growth factor in PC3 cells cultured in serum-free medium did not increase the IC50 values. Suramin was active against these 6 cell lines at clinically achievable concentrations. This activity varied depending on the cell line, exposure time and suramin concentration. The most significant factor interfering with sensitivity to suramin was the amount of protein present in the culture medium.
Insights
Suramin exhibits antiproliferative effects against various cancer cell lines. Its efficacy is influenced by protein concentration in culture media, with higher protein levels reducing suramin
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Suramin demonstrates antiproliferative activity by interfering with growth factor signaling and cellular enzymes.
- Understanding suramin's activity across different cancer types and treatment conditions is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the impact of various factors on suramin's antiproliferative activity in diverse cancer cell lines.
- To determine optimal conditions for suramin treatment, considering cell line, exposure time, and media composition.
Main Methods:
- Cultured six cancer cell lines (MCF-7, MCF-7/ADRR, PC3, HT-29, UM-SCC-11B, SW-1573/IR500) with varying suramin exposure times and concentrations.
- Assessed suramin's efficacy in media supplemented with fetal calf serum (FCS), human serum albumin (HSA), and growth factors like epidermal growth factor (EGF).
- Measured the concentration of suramin required for 50% growth inhibition (IC50) under different experimental conditions.
Main Results:
- Suramin's IC50 varied significantly across cell lines, ranging from 45 microM to over 0.5 mM.
- Reduced FCS concentrations (0.5-1%) markedly decreased suramin's IC50, enhancing its sensitivity.
- Increased protein concentrations (FCS and HSA) elevated suramin's IC50, indicating reduced efficacy.
Conclusions:
- Suramin exhibits clinically achievable antiproliferative activity against multiple cancer cell lines.
- Protein content in culture media is a critical determinant of suramin's sensitivity.
- Optimizing suramin treatment requires careful consideration of exposure duration and protein levels in the surrounding environment.