Protamine sulfate inhibition of serum-induced mitogenic responses: differential effects on normal and neoplastic cells
Leibovich, S.J.; Polverini, P.J.
Journal of the National Cancer Institute 73(6): 1337-1347
1984
ISSN/ISBN: 0027-8874 PMID: 6210390 Document Number: 222684
Protamine sulfate reversibly inhibits serum-induced mitogenic stimulation of several nontransformed and neoplastic cell types in vitro. Fifty percent inhibition was induced by approximately 120-150 micrograms protamine sulfate/ml. Cells were affected directly, and inhibition depended on the duration of cell exposure. Heparin, chondroitin sulfate, heparan sulfate, and dextran sulfate neutralized protamine sulfate effects during the early stages of treatment. Nontransformed cells [bovine aortic endothelial cells, adult human gingival fibroblasts (strains 423 and 1101), fetal rat skin (strain 921-K) and muscle fibroblasts] required longer exposure to induce inhibition than did neoplastic cells [rat 3-methylcholanthrene-induced fibrosarcoma cell lines (MCA-6 and MCA-9), a macrophage-like cell line (NCTC-3749), Walker 256 rat carcinoma cells (ATCC-CCL-38), rat Morris hepatoma cells (ATCC-CCL-144), murine melanoma cells (B16), and rat bladder squamous cell carcinoma cells (804-G)]. Other polycationic compounds, including histone type VIII-S, poly-L-lysine, poly-L-arginine, and protamine (free base), were also effective inhibitors, whereas the basic proteins cytochrome c and lysozyme had no effect. Poly-L-histidine, poly-L-glutamic acid, poly-L-aspartic acid, and dextran blue also had no inhibitory effect.