Swainsonine, an inhibitor of alpha-
mannosidases, has been shown to block experimental
metastasis of B16F10
melanoma and MDAY-D2 lymphoid
tumor cells in syngeneic mice. In this report we demonstrate that
swainsonine also reduces the growth rate of human
melanoma cells in vitro and in vivo. Graded doses of
swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo
melanoma cells.
Swainsonine at 10 micrograms/ml in the
drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the MeWo
tumors by approximately 50% and inhibited the expression of complex-type
oligosaccharides in
tumors and host intestine by only 10-20%.
Swainsonine doses of 4 mg/kg/day reduced expression of complex-type
oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type
asparagine-linked
oligosaccharides resulting in incomplete processing similar to that observed in
swainsonine-treated MeWo
tumor cells.
Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5
tumors in nude mice. The results suggest that expression of highly branched complex-type
oligosaccharides commonly associated with the malignant phenotype may provide the
tumor cells with a growth advantage.