Antiproliferative effects of suramin on androgen responsive tumour cells.

Overview

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.