Antiproliferative effect of suramin on primary cultures of human pheochromocytomas and rat PC12 pheochromocytoma cells.
Suramin inhibits growth of neural crest-derived cells and is used to treat adrenocortical cancer and neuroblastoma in clinical trials. The antiproliferative effect of suramin was evaluated in primary cultures of human pheochromocytoma and the PC12 rat pheochromocytoma cell line in vitro and in vivo. Human pheochromocytoma and PC12 rat pheochromocytoma cells were grown in medium supplemented with suramin at concentrations of 1-1,000 micrograms/ml (1.43-1.43 mM) for up to five generations. Suramin did not induce neuronal differentiation, but inhibited growth of cultured human pheochromocytoma cells with IC50 (inhibitory concentration at which a 50% reduction of proliferation is observed) of 50-250 micrograms/ml. Also, suramin inhibited proliferation of PC12 cells with IC50 of 228 micrograms/ml after 5 days and 161 micrograms/ml at 10 days of treatment. Colony formation assays demonstrated these effects to be cytotoxic rather than cytostatic. Thus when reproductive integrity of PC12 cells was taken into account, IC50 was calculated with 118 micrograms/ml and 129 micrograms/ml, respectively. In vivo experiments were performed with subcutaneously xenotransplanted PC12 cells (BALB/c NCR-NU mice). Suramin did not alter tumorigenicity and did not inhibit local tumor growth. These data determine for the first time an antiproliferative effect of suramin in pheochromocytoma cells. Suramin is cytotoxic to pheochromocytoma cells in vitro at levels that are clinically achievable. Suramin may have potential as an antiproliferative drug in nonresectable pheochromocytoma.