3 '-azidothymidine significantly alters glycosphingolipid synthesis in melanoma cells and decreases the shedding of gangliosides

In this report, we establish that 3'-azido-3'-deoxythymidine (AZT) treatmen t of melanoma cells greatly alters the pattern of glycosphingolipid biosynt hesis. In SK-MEL-30 cells, synthesis of the gangliosides GM3 and GD3 was si gnificantly inhibited (60% and 50% of control, respectively) and the produc tion of their precursor, lactosylceramide, was stimulated by 2.5-fold. Cont rol experiments established that phospholipid synthesis was not affected by AZT treatment, consistent with AZT treatment only affecting lipid biosynth etic reactions that involve glycosylation. Likely as a consequence of decre ased rates of ganglioside synthesis, AZT treatment of SK-MEL-30 cells also significantly suppressed the amount of gangliosides shed from the membranes of these cells. Since shedding of gangliosides has been proposed to allow melanoma cells to avoid destruction by the immune system and alterations of glycosphingolipid levels are likely important for the malignant cell pheno type, these results may have important implications regarding the potential use of AZT or related glycosylation inhibitors as cancer chemotherapeutics .