Suramin is a potent inhibitor of calcemic hormone- and growth factor-induced bone resorption in vitro.
Suramin, a polysulfonated naphtylurea compound that has been used in the past for treatment of trypanosomiasis and onchocerciasis, is also an effective antitumor agent. Its marked antiproliferative potential probably resides in the ability of the drug to interfere with various growth factor signaling mechanisms. We were interested in whether suramin could also interact with signal transduction in bone cells, leading to osteoclast proliferation and, consequently, bone resorption. Utilizing organ-cultured neonatal mouse calvaria, we studied the effect of suramin on bone resorption induced by, for example, parathyroid hormone, 1,25-dihydroxycholecalciferol, epidermal growth factor or thrombin. In the 1 to 100 microM concentration range, in which no toxic effect on bone cells was observed, suramin effectively suppressed bone resorption regardless of whether it was mediated by endogenous prostaglandin production or induced by parathyroid hormone (Ki = 70 microM), 1,25-dihydroxycholecalciferol (Ki = 70 microM), epidermal growth factor (Ki = 5 microM) or thrombin (Ki = 5 microM). The profound inhibitory effect of suramin on various bone resorptive processes around 100 microM, which is regarded as the minimally effective concentration for successful anticancer treatment, could be exploited for the treatment particularly of tumors associated with hypercalcemia.
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
K H
KH
Farsoudi
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P
Pietschmann
H S
HS
Cross
M
M
Peterlik
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000517:prevention & control*; D002117:Calcitriol / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D013498:Suramin / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D010281:Parathyroid Hormone; D011453:Prostaglandins; D013498:Suramin; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D013917:Thrombin; D002117:Calcitriol