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Suramin inhibits vasoactive intestinal peptide (VIP) binding and VIP-induced cAMP accumulation into two human
1Institut de Chimie Biologique, CNRS URA 202, Université D'Aix-Marseille I, France.
Abstract:
The antihelminthic drug suramin inhibits the binding of monoradioiodinated VIP (125I-VIP) to two human cancerous cell lines, namely HT 29-D4 and IGR 39 derived from a colic adenocarcinoma and a superficial melanoma respectively, with an IC50 of 280 micrograms/ml. The drug is not able to remove 125I-VIP previously bound to either types of cells even with concentration as high as 1500 micrograms/ml. Neither 125I-VIP binding nor VIP binding sites molecular weight are affected by pretreatment of the cells by the drug. Suramin at 1000 micrograms/ml inhibits by 56% to 99% the cAMP accumulation induced by VIP, depending on the VIP concentrations and the cell lines used for the experiments. On the contrary the drug does not have any effects on the cAMP accumulation induced by the beta receptor agonist isoproterenol. Also suramin does not affect the basal accumulation of cAMP in both types of cells either in acute or chronic treatment with the drug. We speculate that these observations may account, at least in part, for the in vivo and in vitro effects of VIP and suramin on cell proliferation and survival.
Insights
The antihelminthic drug suramin inhibits vasoactive intestinal peptide (VIP) binding to cancer cells and blocks VIP-induced cAMP accumulation. This suggests suramin
Area of Science:
- Pharmacology
- Cancer Biology
- Cell Signaling
Background:
- Vasoactive intestinal peptide (VIP) plays a role in cell proliferation and survival.
- Cancer cells express VIP receptors, making them potential targets for VIP-related therapies.
Purpose of the Study:
- To investigate the effects of the antihelminthic drug suramin on VIP binding and signaling in human cancer cell lines.
- To determine if suramin interferes with VIP-induced cellular responses.
Main Methods:
- Experiments were conducted using two human cancer cell lines: HT 29-D4 (colic adenocarcinoma) and IGR 39 (superficial melanoma).
- Monoradioiodinated VIP (125I-VIP) binding assays were performed to assess suramin's inhibitory effects.
- Cyclic adenosine monophosphate (cAMP) accumulation assays were used to measure VIP-induced signaling.
- The effects of suramin on isoproterenol-induced cAMP accumulation and basal cAMP levels were also evaluated.
Main Results:
- Suramin inhibited 125I-VIP binding to both cell lines with an IC50 of 280 µg/ml.
- Suramin did not displace pre-bound 125I-VIP or affect VIP receptor molecular weight.
- Suramin significantly inhibited VIP-induced cAMP accumulation (56-99%) in a dose- and cell-dependent manner.
- Suramin had no effect on isoproterenol-induced cAMP accumulation or basal cAMP levels.
Conclusions:
- Suramin interferes with VIP binding to cancer cells and inhibits VIP-mediated cAMP signaling.
- These findings suggest a potential mechanism for suramin's observed effects on cancer cell proliferation and survival.
- Suramin's specific inhibition of VIP signaling warrants further investigation in cancer therapy.