The effects of glycosylation inhibitors on the proliferation of a Wilms tumour cell line.
We have examined the effects of different glycosylation inhibitors on the proliferation of a human Wilms tumour derived cell line WCCS-1. It was found that two compounds that specifically inhibit distal steps in the glycosylation chain (swainsonone and castanospermine) only exerted marginal effects on cell multiplication and survival. In contrast, a proximal inhibitor (tunicamycin) efficiently increased necrosis in a dose dependent fashion. It is shown that this cell death was accompanied by a marked decrease in the incorporation of glucosamine, but rather unexpectedly, only caused a limited inhibition of de novo protein synthesis. Moreover, the entrance into S-phase was virtually unchanged in the cells surviving the exposure to tunicamycin. The effects of tunicamycin on cell multiplication and survival could not be reversed by concomitant addition of mevalonate as has been shown in other cell lines. Taken together this data suggests that tunicamycin does not operate in a cell cycle specific manner in Wilms tumour cells.
Granerus
M
M
Department of Pathology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Engström
W
W
D000970:Antineoplastic Agents / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006031:Glycosylation; D006801:Humans; D007212:Indolizines / Q000633:toxicity*; D007680:Kidney Neoplasms; D007700:Kinetics; D008798:Mevalonic Acid / Q000494:pharmacology; D009336:Necrosis; D017026:Swainsonine / Q000633:toxicity*; D014415:Tunicamycin / Q000633:toxicity; D009396:Wilms Tumor; D054836:Indolizidines
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007212:Indolizines; D008798:Mevalonic Acid; D017026:Swainsonine; D014415:Tunicamycin; C037806:castanospermine; D054836:Indolizidines