Suramin inhibits the growth of non-small-cell lung cancer cells that express the epidermal growth factor receptor.
The epidermal growth factor (EGF) is a potent growth factor that is believed to enhance the proliferation of cancer cells by a paracrine or autocrine mechanism. EGF transduces various signals and finally stimulates cell proliferation upon binding to cell surface receptors. Prevention of the association of this peptide with its receptors might lead to the development of new modalities for treatment of lung cancer. Several investigators have reported that suramin has antiproliferative activity against cancer cells that express EGF receptors (EGF-R), and that it acts by blocking the binding of the ligand to its receptor. In this study, we analyzed the antitumor effect of suramin using two lines of lung cancer cells (A549 and PC-13), which express EGF-R, and a variety of assays. Receptor-binding assays confirmed that A549 and PC-13 cells have cell surface receptors for EGF. Suramin inhibited the binding of EGF to these receptors. EGF and fetal bovine serum (FBS) stimulated the proliferation of cells, but suramin inhibited these effects in a dose-dependent fashion. Suramin at 200 microg/ml reduced the growth of A549 and PC-13 cells by 25 and 15%, respectively, in medium that contained 1% FBS. Paradoxically, the concentrations of suramin that inhibited cell proliferation were lower than those that were effective in inhibiting the binding of EGF to its receptor. Although expression of c-fos and c-myc mRNA increased when cells were stimulated by EGF or FBS, suramin at 200 microg/ml did not markedly alter such expression. Suramin partially blocked the EGF- induced progression of the cell cycle from the G0/G1 to the S phase. These results suggest that suramin partially blocks EGF signal transduction. Suramin probably inhibits cell proliferation by inhibiting intranuclear enzymes, as well as by partial blockage of EGF signal transduction.[1]References
- Suramin inhibits the growth of non-small-cell lung cancer cells that express the epidermal growth factor receptor. Fujiuchi, S., Ohsaki, Y., Kikuchi, K. Oncology (1997) [Pubmed]
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