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Polysulfated heparinoids selectively inactivate heparin-binding angiogenesis factors
G Zugmaier1, R Favoni, R Jaeger
1Department of Hematology/Oncology, Philipps-University, Marburg, Germany.
Annals of the New York Academy of Sciences
|February 10, 2000
Summary
Polysulfated heparinoids selectively inhibit fibroblast growth factors (FGF) crucial for tumor growth and metastasis. These compounds offer a promising, targeted approach to blocking angiogenesis in cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Angiogenesis is essential for tumor expansion and metastasis.
- Heparin-binding growth factors, like acidic and basic fibroblast growth factor (FGF), promote angiogenesis.
- Targeting FGF signaling is a potential anti-cancer strategy.
Purpose of the Study:
- To investigate the inhibitory effects of suramin and polysulfated heparinoids (pentosan polysulfate, dextran sulfate, fucoidan) on FGF action.
- To evaluate the selectivity of these inhibitors against FGF-induced tumor cell growth.
Main Methods:
- Utilized the SW 13 adrenal cancer cell line, dependent on FGF for anchorage-independent growth.
- Assessed the inhibition of FGF-induced growth and receptor binding.
- Compared inhibitory effects against insulin-like growth factor 1 (IGF-1) and transforming growth factor alpha (TGF-α).
Main Results:
- Polysulfated heparinoids inhibited FGF-induced growth and binding with an IC50 of 0.5-3 µg/ml.
- Suramin inhibited FGF at a much higher IC50 of 100 µg/ml.
- Heparinoids were selective, showing no effect on IGF-1 or TGF-α, while suramin inhibited these growth factors at 100 µg/ml.
Conclusions:
- Polysulfated heparinoids selectively inhibit heparin-binding angiogenic factors at significantly lower concentrations than suramin.
- Suramin acts as a non-selective inhibitor of growth factors.
- Polysulfated heparinoids represent a novel therapeutic strategy for cancer by blocking angiogenesis.