Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of determined Asn-bound glycans (N-glycans) in cell surface glycoproteins regulates different processes in tumour cell biology. Specific patterns of N-glycosylation are displayed by highly metastatic cells and it has been shown that inhibition of N-glycan processing restrains cell proliferation and induces cell death via apoptosis. However, the mechanisms by which different N-glycosylation states may regulate cell viability and growth are not understood. Since malignant cells express high levels of intracellular glutathione (GSH) and a reduction of intracellular GSH induces cell death via apoptosis, we investigated whether GSH was involved in the induction of apoptosis by removal of cell surface N-glycans. We found that removal of N-glycans from cell surface proteins by treating the rhabdomyosarcoma cell line S4MH with tunicamycin or N-glycosidase resulted in a reduction in intracellular GSH content and cell death via apoptosis. Moreover, GSH depletion caused by the specific inhibitor of GSH synthesis BSO induced apoptosis in S4MH cells. This data indicates that adequate N-glycosylation of cell surface glycoproteins is required for maintenance of intracellular GSH levels that are necessary for cell survival and proliferation.
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PMID:Removal of N-glycans from cell surface proteins induces apoptosis by reducing intracellular glutathione levels in the rhabdomyosarcoma cell line S4MH. 1137 42

Glutathione (GSH) is involved in many cellular functions, including cell growth and differentiation. GSH also plays an important role in the protection of cells against oxidative damage and hence in determining the sensitivity of cells to the cytotoxicity of anticancer agents. Because of this, induction of GSH depletion has been proposed as a good strategy for sensitizing tumor cells to antitumor agents. The aim of the present work is to study the effect of buthionine sulfoximine (BSO, a specific cellular GSH-depleting agent) in two rat tumor cell lines derived from the same rhabdomyosarcoma tumor model, the moderately differentiated and low metastatic F21 cell line, and the poorly differentiated and high metastatic S4MH cell line, to investigate the influence of the degree of differentiation in the induction of GSH depletion-based therapy. We observed that, whereas in the S4MH cell line BSO induced a dose-dependent inhibition of both cell growth in vitro and tumorigenic potential in vivo, in F21 cells the administration of moderate doses of BSO enhanced tumor growth and only at high doses was there a slight reduction of their tumorigenic potential. These effects were in consonance with the fact that the activity of gamma-glutamyltranspeptidase (gamma-GT) present in the F21 cells was 4 times higher than in the S4MH cells. Indeed, inhibition of gamma-GT activity by acivicin not only abrogated the BSO-induced increase of GSH content and of cell growth, but also the combination of acivicin + BSO significantly decreased intracellular GSH levels and cell proliferation, and induced F21 cells to apoptosis. These studies suggest that, as occurs in the rhabdomyosarcoma tumor model, gamma-GT levels and the degree of differentiation of tumor cells might influence the response of tumor cells to inducers of GSH depletion, and should be taken into account in therapies based on GSH metabolism.
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PMID:Role of gamma-glutamyltranspeptidase on the response of poorly and moderately differentiated rhabdomyosarcoma cell lines to buthionine sulfoximine-induced inhibition of glutathione synthesis. 1198 72