Swainsonine is an indolizidine alkaloid naturally found in certain plants including locoweed that inhibits N-linked glycoside hydrolases, preventing the processing of asparagine-linked glycoproteins. It reversibly inhibits lysosomal α-mannosidase and Golgi α-mannosidase II (IC50 = 0.2 μM).[1] Swainsonine is used to study the role of N-linked glycosylation in cellular processes and has been shown to have antiproliferative and antimetastatic effects on cancer cells in culture and in mice.[2],[3],[4] The inhibition of α-mannosidase activity in lysosomes produces an accumulation of partially-processed oligosaccharides and glycoproteins, giving rise to lysosomal storage disease. Swainsonine toxicity in herbivores results in a condition known as locoism, characterized by hyperactivity, aggression, stiff and clumsy gait, low head carriage, salivation, seizures, and apparent blindness, culminating in increased miscoordination, weakness and death.
Reference:
[1]. Tulsiana, D.R.P., Broquist, H.P., and Touster, O. Marked differences in the swainsonine inhibition of rat liver lysosomal α-D-Mannosidase, Rat Liver Golgi Mannosidase II, and Jack Bean α-D-Mannosidase. Archives of Biochemistry and Biophysics 236, 427-434 (1985).
[2]. Dennis, J.W., Koch, K., Yousefi, S., et al. Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine. Cancer Research 50, 1867-1872 (1990).
[3]. Reddy, B.V.V.G., and Kalraiya, R.D. Sialilated β1,6 branched N-oligosaccharides modulate adhesion, chemotaxis, and motility of melanoma cells: Effect on invasion and spontaneous metastasis properties. Biochimica et Biophysica Acta 1760, 1393-1402 (2006).
[4]. Sun, J.Y., Zhu, M.Z., Wang, S.W., et al. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine. Phytomedicine 14, 353-359 (2007).