Suramin suppresses hypercalcemia and osteoclastic bone resorption in nude mice bearing a human squamous cancer.
Suramin is a polyanionic agent which has been found to be an effective antineoplastic agent against various human tumors including adrenal, renal and prostatic cancer, and osteosarcoma. Recently, suramin has been shown to inhibit bone resorption in organ cultures of mouse calvarial bones. In the present study, we examined the effects of suramin on increased osteoclastic bone resorption and hypercalcemia in nude mice bearing a human oral squamous carcinoma. Suramin (1 mg/mouse/injection) was administered i.p. three times a week for the first 2 weeks and then once weekly for the next 6 weeks. Blood ionized calcium levels in the suramin-treated cancer-bearing group were significantly lower than those in the untreated cancer-bearing group. Histological and histomorphometrical examination of bones of these animals showed a significant decrease in osteoclast numbers in the suramin-treated cancer-bearing animals. Suramin at a dose of 0.1 mg/mouse/injection was ineffective and 2 mg/mouse/injection was toxic, confirming its narrow effective dose. Suramin showed no effects on the growth of this squamous cancer. However, suramin markedly inhibited in vivo growth of a rat prostatic adenocarcinoma. In mouse marrow cultures, suramin decreased osteoclast-like cell formation in a dose-dependent manner. Furthermore, suramin also inhibited bone resorption in organ cultures of fetal rat long bones and resorption pit formation by isolated mature rat osteoclasts. These results show that suramin is an effective inhibitor of osteoclastic bone resorption in vitro and in vivo and suggest that suramin may be a useful agent in prevention and treatment of cancer-induced hypercalcemia. However, our results also suggest that for this indication suramin has a confined range of effective dose.
Yoneda
T
T
Department of Medicine, University of Texas Health Science Center at San Antonio 78284, USA.
Williams
P
P
Rhine
C
C
Boyce
B F
BF
Dunstan
C
C
Mundy
G R
GR
D000230:Adenocarcinoma / Q000097:blood / Q000150:complications; D000818:Animals; D001862:Bone Resorption / Q000097:blood* / Q000188:drug therapy*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000150:complications*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D008175:Lung Neoplasms / Q000097:blood* / Q000150:complications*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000097:blood / Q000150:complications; D051381:Rats; D013498:Suramin / Q000494:pharmacology*
D013498:Suramin; D002118:Calcium