Suramin disrupts insulin-like growth factor-II (IGF-II) mediated autocrine growth in human SH-SY5Y neuroblastoma cells.
Suramin, traditionally used in the treatment of trypanosomiasis, is under investigation in the treatment of cancer. One side effect that limits its use is the onset of a sensorimotor polyneuropathy. In order to investigate the mechanism by which suramin induces polyneuropathy, we examined its effects on SH-SY5Y human neuroblastoma cells, an in vitro model of neuronal growth and differentiation. Addition of 50-400 micrograms/ml suramin to SH-SY5Y cells grown in 0.6% CS inhibited [3H]thymidine ([3H]TdR) incorporation and cell growth. Upon removal of suramin, [3H]TdR incorporation increased, demonstrating that levels of suramin used were cytostatic and not cytotoxic. Analysis of suramin-treated SH-SY5Y cells by flow cytometry revealed growth arrest in the G1/G0 phase of the cell cycle. IGF-II-induced SH-SY5Y growth is mediated by the type I IGF receptor (IGF-IR). Therefore, we examined its effect on IGF-IR tyrosine phosphorylation. Suramin prevented IGF-II-stimulated IGF-IR tyrosine phosphorylation. These results indicate that in SH-SY5Y cells, suramin acts as a cytostatic agent and can block IGF-II-dependent cell growth by preventing IGF-IR activation. Thus, suramin toxicity in the peripheral nervous system may be due, in part, to preventing IGF and other growth factors from activating their receptors.
Sullivan
K A
KA
Department of Internal Medicine, University of Michigan, Ann Arbor, 48109-0588, USA.
Kim
B
B
Buzdon
M
M
Feldman
E L
EL
D001932:Brain Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects*; D005956:Glucose-6-Phosphate Isomerase / Q000187:drug effects*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013498:Suramin; D007335:Insulin-Like Growth Factor II; D005956:Glucose-6-Phosphate Isomerase