Effects of suramin on the proliferation of primary epithelial cell cultures derived from normal, benign hyperplastic and cancerous human prostates.
Primary epithelial cultures (PECs) derived from normal, benign hyperplastic (BPH), and cancerous human prostate tissue were treated with increasing doses of suramin, and assayed for cell proliferation over a period of days. The suramin IC50 (inhibitory concentration 50%) value was 0.5 to 1.0 x 10(-4) M, whereas doses between 2.5 x 10(-4) and 5 x 10(-4) M resulted in total growth inhibition. This inhibition was reversible by exchange with suramin-free medium up to day 6. Concentrations > or = 5 x 10(-4) M resulted in increased cytotoxicity as exposure time increased. No differential response to suramin could be demonstrated among the prostate PECs derived from different tissues. The established cell lines, PC-3 and DU 145, grown in serum containing medium exhibited IC50s comparable to the PECs grown in serum free medium. EGF, bFGF, alpha, or beta ECGF at the concentrations tested did not reverse suramin inhibition. Increasing concentrations of bovine pituitary extract (BPE) increased cell growth in both the treated and the control cells. However, the percent growth inhibition by suramin at each concentration of BPE remained constant. Flow cytometry examination of cells treated for 7 days with suramin (0-10(-3) M) failed to detect any significant cell cycle alterations compared to control. At high concentrations of suramin (> or = 10(-4) M), large numbers of viable and dead cells were detectable in the medium. The increase in unattached viable cells was most prevalent (80%) in cultures treated with suramin at the time of plating, but also occurred with cells (25-30%) plated hours prior to the addition of suramin. Treatment for several days with low concentrations of suramin (10(-7) to 10(-5) M) transiently enhanced cell growth compared to controls.
Mitchen
J
J
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Rago
R
R
Wilding
G
G
D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D005434:Flow Cytometry; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects*; D011470:Prostatic Hyperplasia / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology*
D006133:Growth Substances; D013498:Suramin