Antiproliferative effects of suramin on androgen responsive tumour cells.
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.


CONCLUSIONS
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.
Berns
E M
EM
Division of Endocrine Oncology, Dr Daniel de Hoed Cancer Center, Rotterdam, The Netherlands.
Schuurmans
A L
AL
Bolt
J
J
Lamb
D J
DJ
Foekens
J A
JA
Mulder
E
E
D000726:Androgen Antagonists; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D005834:Genital Neoplasms, Male / Q000473:pathology; D006131:Growth Inhibitors; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007890:Leiomyosarcoma / Q000473:pathology; D008297:Male; D015741:Metribolone / Q000037:antagonists & inhibitors; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology*; D013739:Testosterone / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014649:Vas Deferens
D000726:Androgen Antagonists; D006131:Growth Inhibitors; D006133:Growth Substances; D015741:Metribolone; D013739:Testosterone; D013498:Suramin