Suramin inhibits vasoactive intestinal peptide (VIP) binding and VIP-induced cAMP accumulation into two human cancerous cell lines.
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.
Bellan
C
C
Institut de Chimie Biologique, CNRS URA 202, Université D'Aix-Marseille I, France.
Pic
P
P
Marvaldi
J
J
Fantini
J
J
Pichon
J
J
D003432:Cross-Linking Reagents; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D011485:Protein Binding; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry; D018005:Receptors, Vasoactive Intestinal Peptide; D013388:Succinimides; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D007457:Iodine Radioisotopes; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D013388:Succinimides; D014660:Vasoactive Intestinal Peptide; D013498:Suramin; D000242:Cyclic AMP; D007545:Isoproterenol; C019358:disuccinimidyl suberate