Topic
Swainsonine
About: Swainsonine is a research topic. Over the lifetime, 489 publications have been published within this topic receiving 13662 citations. The topic is also known as: (1S,2R,8R,8AR)-octahydro-1,2,8-indolizinetriol & Tridolgosir.
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441 citations
TL;DR: In this article, the indolizidine alkaloids swainsonine and noxide have been identified as constituents of spotted locoweed and the inhibition of lysosomal α-mannosidase by these alkaloid compounds has been investigated.
Abstract: The indolizidine alkaloids swainsonine and swainsonine N-oxide have been isolated and identified as constituents of spotted locoweed. The inhibition of lysosomal α-mannosidase by these alkaloids su...
389 citations
TL;DR: In this article, a potent inhibitor of α-mannosidase was isolated from Swainsona canescens and was shown to be an indolizidinetriol by spectroscopic techniques and the relative stereochemistry was defined as 8aβ-indolizidine-lα,2α,8β-triol.
Abstract: A potent inhibitor of α-mannosidase was isolated from Swainsona canescens. The inhibitor was shown to be an indolizidinetriol by spectroscopic techniques and the relative stereochemistry was defined as 8aβ-indolizidine-lα,2α,8β-triol.
387 citations
TL;DR: Evidence is presented to suggest that swainsonine is a reversible active site-directed inhibitor of lysosomal alpha-mannosidase.
Abstract: An indolizidine alkaloid (swainsonine) was isolated from the plant Swainsona canescens. Swainsonine is a specific and potent inhibitor of alpha-mannosidase (EC 3.2.1.24) and when administered to animals produces a phenocopy of the genetically based lysosomal storage disease, mannosidosis. Evidence is presented to suggest that swainsonine is a reversible active site-directed inhibitor of lysosomal alpha-mannosidase.
346 citations
Journal Article•
TL;DR: The antimetastatic effect of tunicamycin may be related to interference in tumor cell-extracellular matrix interactions, whereas treatment with castanospermine or swainsonine appears to block at a stage distal to initial tumor cell arrest.
Abstract: The extent of maturation of the oligosaccharide subunits of tumor cell glycoproteins appears to correlate with malignant potential, suggesting that modification of oligosaccharide structures may alter metastatic capacity. Castanospermine, a recently discovered inhibitor of glucosidase I, was tested for its effect on experimental metastasis of B16-F10 murine melanoma cells and was compared to treatment with swainsonine and tunicamycin. All three drugs block different steps in the pathway of glycoprotein processing yet each was a potent inhibitor of pulmonary colonization after i.v. injection of treated cells into C57BL/6 mice (greater than or equal to 80% inhibition). This result indicates a generality of inhibition of experimental metastasis by blockage of protein glycosylation or oligosaccharide processing and strongly implicates carbohydrate residues in at least one critical step of the metastatic cascade. Cytotoxic side effects could not account for the inhibitory activity. In order to identify a possible mechanism of inhibition of colonization, the adhesive behavior and pulmonary retention properties of B16-F10 cells treated with the above inhibitors were examined. Tunicamycin-treated B16-F10 cells exhibited poor adhesion to substrate-adsorbed fibronectin and laminin, whereas both castanospermine- and swainsonine-treated cells possessed near normal adhesive capacity; furthermore, the initial rate of loss of tunicamycin-treated cells from the lungs of mice was substantially greater than either control, castanospermine- or swainsonine-treated cells. These data suggest that these processing inhibitors can block experimental metastasis by at least two different mechanisms. The antimetastatic effect of tunicamycin may be related to interference in tumor cell-extracellular matrix interactions, whereas treatment with castanospermine or swainsonine appears to block at a stage distal to initial tumor cell arrest.
311 citations