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Antiproliferative effects of suramin on androgen responsive tumour cells
E M Berns1, A L Schuurmans, J Bolt
1Division of Endocrine Oncology, Dr Daniel de Hoed Cancer Center, Rotterdam, The Netherlands.
Unlabelled:
The effect of the polyanionic drug suramin on two androgen responsive tumour cell lines was studied. Human prostate tumour (LNCaP) cell growth is stimulated two- to three-fold by the synthetic androgen R1881 (0.1 nM) or EGF (1 ng/ml). Suramin (0.01-1.0 mM) inhibited the growth of LNCaP cells in a dose dependent way, both in the presence and absence of androgen or EGF. Growth was arrested in the G0/G1 phase of the cell cycle, but was resumed after removal of suramin. DDT-1 hamster ductus deferens tumour cells are stimulated by PDGF (25 ng/ml), b-FGF (10 ng/ml) and testosterone (10 nM). Suramin inhibited PDGF and b-FGF stimulated cell growth. However in the presence of testosterone, suramin showed a biphasic effect: stimulatory at low dose (0.01 mM) and inhibitory above 0.01 mM. Suramin decreased the apparent affinity of EGF binding sites on LNCaP cells with a two- to eight-fold increase in Kd at 0.1 and 1.0 mM suramin, respectively.
In Conclusion:
suramin counteracts the growth stimulatory effects of both androgens and growth factors on androgen sensitive tumour cells. The effects are reversible after withdrawal of suramin.
Insights
Suramin, a polyanionic drug, effectively inhibits androgen and growth factor-stimulated tumor cell proliferation. These anti-proliferative effects are reversible upon drug withdrawal, offering potential therapeutic insights.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Androgen-responsive tumors, such as prostate cancer, rely on androgens and growth factors for proliferation.
- Targeting these signaling pathways is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the effects of the polyanionic drug suramin on androgen-responsive tumor cell lines.
- To determine suramin's impact on cell growth, cell cycle progression, and receptor binding affinities.
Main Methods:
- Cultured human prostate tumor (LNCaP) and DDT-1 hamster ductus deferens tumor cells.
- Administered suramin at varying concentrations (0.01-1.0 mM) with or without androgens (R1881, testosterone) or growth factors (EGF, PDGF, b-FGF).
- Assessed cell proliferation, cell cycle phase distribution (G0/G1 arrest), and epidermal growth factor (EGF) binding affinity (Kd).
Main Results:
- Suramin dose-dependently inhibited LNCaP cell growth stimulated by androgens or EGF, arresting cells in G0/G1 phase.
- Suramin also inhibited PDGF and b-FGF stimulated growth in DDT-1 cells.
- A biphasic effect of suramin was observed in testosterone-stimulated DDT-1 cells (stimulatory at 0.01 mM, inhibitory at higher concentrations) and suramin decreased EGF binding affinity in LNCaP cells.
Conclusions:
- Suramin counteracts the growth-stimulatory effects of androgens and growth factors on androgen-sensitive tumor cells.
- The observed anti-proliferative effects of suramin are reversible after its withdrawal.
- Suramin's ability to inhibit key growth pathways suggests its potential as an anti-cancer agent.