Antiproliferative effects of suramin on androgen responsive tumour cells

Eur J Cancer. 1990 Apr;26(4):470-4. doi: 10.1016/0277-5379(90)90018-o.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen Antagonists*
  • Animals
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cricetinae
  • Drug Screening Assays, Antitumor
  • Genital Neoplasms, Male / pathology
  • Growth Inhibitors
  • Growth Substances / metabolism
  • Humans
  • Leiomyosarcoma / pathology
  • Male
  • Metribolone / antagonists & inhibitors
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Suramin / pharmacology*
  • Testosterone / antagonists & inhibitors
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Vas Deferens

Substances

  • Androgen Antagonists
  • Growth Inhibitors
  • Growth Substances
  • Metribolone
  • Testosterone
  • Suramin