Suramin inhibits bone resorption and reduces osteoblast number in a neonatal mouse calvarial bone resorption assay.
The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose-dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis.
Walther
M M
MM
Urologic Oncology Section, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892.
Kragel
P J
PJ
Trahan
E
E
Venzon
D
D
Blair
H C
HC
Schlesinger
P H
PH
Jamai-Dow
C
C
Ewing
M W
MW
Myers
C E
CE
Linehan
W M
WM
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology*; D001345:Autoradiography; D001862:Bone Resorption / Q000503:physiopathology*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D011392:Proline / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology; D012886:Skull / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003470:Culture Media; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D013498:Suramin; D004815:Epidermal Growth Factor; D002116:Calcitonin; D011392:Proline; D000469:Alkaline Phosphatase; D002118:Calcium