Sodium cyanate is a selective inhibitor of
protein synthesis in a variety of mammalian
tumor cells without a corresponding effect on normal tissue of the
tumor-bearing animals. In the present study, we investigated the potential role of
sodium cyanate in the augmentation of the antitumor activity of
melphalan in MOPC-460D myeloma-bearing BALB/c mice. The simultaneous
intraperitoneal injection of
sodium cyanate, 250 mg/kg, and
melphalan, 12 mg/kg, followed by another dose of
sodium cyanate, 200 mg/kg, administered 18 hours later, resulted in a
tumor growth inhibition index (TGII) of 207%. In contrast,
melphalan or
sodium cyanate administered separately at the same dose induced a TGII of 133% and 15%, respectively, when compared to control animals. Furthermore, a direct comparison of the volume of
tumor implants in mice treated with the combination of
sodium cyanate and
melphalan vs. those treated with
melphalan alone showed a statistically significant growth inhibition in favor of the
sodium cyanate and
melphalan combination on days 35, 39, and 42 from initiation of treatment. The data presented here suggest that the antitumor activity of
melphalan could be increased, with moderate toxicity, by the concomitant intraperitoneal administration of
sodium cyanate in BALB/c mice bearing measurable subcutaneous MOPC-460D
tumor transplants. This is the first report of an increase in
melphalan antitumor activity by
sodium cyanate at a
tumor location distant from the site of injection.