Swainsonine,a glycosylation inhibitor,enhances both lymphocyte efficacy and tumour susceptibility in LAK and NK cytotoxicity |
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| Affiliation: | 1. Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA;2. Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Veterinarstr. 13, Munich, 80539, Germany;1. Laboratory of Pharmacology, Butantan Institute, 05503-000 São Paulo, SP, Brazil;2. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil;3. Department of Physiology, Federal University of São Paulo, 04023-901 São Paulo, SP, Brazil;4. Center of Innovation, Technology and Education (CITE), Anhembi Morumbi University-Laureate International Universities, 12247-016 São José dos Campos, SP, Brazil;1. Dynamics of Immune Responses Unit, Equipe Labéllisée Ligue Contre le Cancer, Institut Pasteur, 75015 Paris, France;2. INSERM U668, rue du Dr Roux, 75015 Paris, France;3. Cellule Pasteur, University Paris Diderot, Sorbonne Paris Cité, 75015 Paris, France;1. CNC − Center for Neurosciences and Cell Biology, University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal;2. FFUC − Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;3. TREAT U, SA − Parque Industrial de Taveiro, Lote 44, 3045-508 Coimbra, Portugal |
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| Abstract: | Swainsonine (SW) inhibits the formation of N-linked complex oligosaccharides and has previously been shown to inhibit experimental metastasis in nude mice models. The present studies with human effector cells have shown that SW enhanced both lymphokine activated killer cell (LAK) and natural killer (NK) cytotoxicity in standard 51Cr-release assays. SW also increased the susceptibility of human K562 and Colo 320 target cells to NK and LAK cytotoxicity. The peak response of both LAK effectors and targets to SW occurred at 1–2 μg/ml SW. A novel finding was that SW enhanced the interleukin 2 (IL-2) β chain receptor subunit expression on both LAK and NK cells to a greater extent than its enhancement of the IL-2Rα (CD25 or TAC) receptor expression on LAK effectors. In addition, increases in both these receptors occurred at the doses of SW which augmented LAK cytotoxicity. We conclude that the anti-metastatic effects of SW have an immunological component which is maximal at 1–2 μg/ml SW. This suggests that dosage may be an important consideration to obtain optimal potential of SW in any future human cancer therapy. |
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