Effects of suramin on human lung cancer cell lines.
Suramin cytotoxicity was studied in a panel of human lung cancer cell lines by the MTT assay. The concentrations of suramin which induced 50% growth inhibition (IC50) ranged from 130 to 3715 microM for the cell lines growing in medium containing 10% fetal calf serum (FCS). In only one cell line was the IC50 at a concentration that can be reached in plasma of patients treated with suramin. Suramin was 18 and 3.3 times more cytotoxic on NCI-N417 cells growing in 2% FCS and in HITES serum-free medium, respectively, than growing in 10% FCS. No difference in suramin cytotoxicity was observed between small and non-small cell lung cancer cell lines. At the lower concentrations tested, suramin stimulated proliferation of the two small cell lung cancer cell lines, NCI-H187 and NCI-N417. Of several growth factors tested, none induced stimulation of growth in NCI-H187 and NCI-N417 cell lines, nor did they in any way alter the stimulatory effect of suramin. Cell counting, DNA flow cytometric analysis and Ki-67 staining confirmed a higher proliferative state in suramin-exposed NCI-H187 cells as compared with untreated cells. However, topoisomerase II-alpha gene expression remained unchanged, as assessed by northern blot analysis and immunostaining. Suramin had an inhibitory effect on topoisomerase II activity, as assessed by the kDNA decatenation assay, with an IC50 of approximately 40 microM. In conclusion, suramin has significant cytotoxic activity in a minority of human lung cancer cell lines, and it stimulates proliferation in some instances. The pleiotropic action of suramin observed should caution on the possibility of tumour acceleration in patients being treated with this drug.
Rubio
G J
GJ
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Pinedo
H M
HM
Virizuela
J
J
van Ark-Otte
J
J
Giaccone
G
G
D015152:Blotting, Northern; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008938:Mitosis / Q000187:drug effects; D013498:Suramin / Q000627:therapeutic use*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D059005:Topoisomerase II Inhibitors; D013498:Suramin