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 be en shown to inhibit bone resorption in organ cultures of mouse calvari al 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 t hen 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 histomo rphometrical examination of bones of these animals showed a significan t 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 do se. Suramin showed no effects on the growth of this squamous cancer. H owever, suramin markedly inhibited in vivo growth of a rat prostatic a denocarcinoma. In mouse marrow cultures, suramin decreased osteoclast- like cell formation in a dose-dependent manner. Furthermore, suramin a lso inhibited bone resorption in organ cultures of fetal rat long bone s and resorption pit formation by isolated mature rat osteoclasts. The se 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 hypercalc emia. However, our results also suggest that for this indication suram in has a confined range of effective dose.