Swainsonine, a glycosylation inhibitor, enhances both lymphocyte efficacy and tumour susceptibility in LAK and NK cytotoxicity.
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 micrograms/ml SW. A novel finding was that SW enhanced the interleukin 2 (IL-2) beta chain receptor subunit expression on both LAK and NK cells to a greater extent than its enhancement of the IL-2R alpha (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 micrograms/ml SW. This suggests that dosage may be an important consideration to obtain optimal potential of SW in any future human cancer therapy.
Galustian
C
C
Academic Surgical Unit, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Foulds
S
S
Dye
J F
JF
Guillou
P J
PJ
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001667:Binding, Competitive; D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003208:Concanavalin A / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D017026:Swainsonine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D017026:Swainsonine