Antitumor activity via inhibition of glycosphingolipid biosynthesis.

The production by cancer cells of glycolipids, perhaps derived partly from host glycolipids, may play essential roles in malignancy, tumor growth, immunity from host immunodefense, and metastasis. The glycolipids are derived from the primary glycolipid, glucosylceramide (GlcCer), which is formed enzymatically from ceramide and uridine diphosphoglucose (UDP-glu). Injection of an inhibitor of this enzyme into mice bearing intraperitoneal Ehrlich ascites tumor cells (EATC) resulted in complete cure of about 30% of the mice and marked prolongation of life in the remainder. Almost all of the surviving mice were immune to a second inoculation of EATC. Injection of GlcCer stimulated cancer cell growth about 50% but this was largely reversed by the inhibitor. This type of inhibitor may have wide application to cancer chemotherapy.