Swainsonine is a plant alkaloid derived from Swainsona canescens (a leguminous plant). It is a reversible, active-site directed inhibitor of a-mannosidase at concentrations of 5-10mM. At acid pH, swainsonine resembles an intermediate in the hydrolysis of mannosidases.
Swainsonine completely inhibits mammalian Golgi a-mannosidase II (a-3/6-mannosidase in the glycoprotein processing pathway) and mammalian lysosomal a-mannosidase (acid mannosidase). At higher concentrations, swainsonine also inhibits mammalian cytosolic a-mannosidase. It has been shown to inhibit growth of transformed fibroblasts in soft agar and to enhance the antiproliferative effects of INF on murine lymphoreticular tumor cells in vitro. It also blocks the expression of b1-6 branched complex-type oligosaccharides and shunts the pathway towards hybrid-type oligosaccharides. Swainsonine does not appear to inhibit secretion or expression of glycoproteins at the cell surface.
Swainsonine is stable for at least 24 h at 37oC in culture media at physiological pH. Working concentration range is 17-1700 ng/ml (0.1-10mM). Swainsonine (at 1 mg/ml) is not cytotoxic and does not inhibit the growth of a variety of mammalian cell lines. Concentrations required to inhibit Golgi a-mannosidase II in vivo may be somewhat higher, as swainsonine tends to concentrate in the acid environment of cell lysosomes, where it exists as a charged cation and does not permeate through membranes readily.
Swainsonine blocks the processing of high-mannose oligosaccharides to complex oligosaccharides. Glycoproteins synthesized in the presence of swainsonine tend to carry mostly high-mannose and hybrid oligosaccharide chains. With short treatments (<24 h) with the inhibitor, cells may retain some complex glycoproteins due to asynchronous cell growth and glycoprotein synthesis.
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