Biomaterial Database

The multidrug resistance modulator SDZ PSC 833 is a potent activator of cellular ceramide formation. 1998

M C Cabot, and T Y Han, and A E Giuliano

John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. cabot@jwci.org

In this study we demonstrate that the multidrug resistance (MDR) modulator PSC 833 is a potent agonist of ceramide metabolism. When added with [3H]serine or [3H]palmitic acid to the culture medium of MCF-7 cells, PSC 833, in a dose-responsive fashion (1-10 microM), increased the levels of [3H]ceramide as much as 16-fold over control. The actual increase in ceramide mass was verified by thin-layer chromatographic chars. Cellular sphingomyelin radioactivity did not decrease during treatment, indicating that PSC 833 does not elicit ceramide formation through a sphingomyelinase pathway. Inclusion of fumonisin B1, an inhibitor of ceramide synthase, blocked formation of ceramide by PSC 833. The results of cell proliferation assays demonstrated a clear correlation between PSC 833 elicitation of ceramide formation and increased cytotoxicity. The MDR modulator and chemical cousin of PSC 833, cyclosporin A, had little impact on cellular ceramide formation. At a concentration of 2.5 microM, cyclosporin A and PSC 833 treatment increased ceramide formation by 20% and 7.5-fold, respectively. These results reveal a new action of PSC 833 which may contribute to its potency as a drug resistance modulator.

UI	MeSH Term	Description	Entries
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002518	Ceramides	Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.	Ceramide
D003524	Cyclosporins	A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection.	Cyclosporines
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D016572	Cyclosporine	A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).	Cyclosporin A,Ciclosporin,CsA-Neoral,CyA-NOF,Cyclosporin,Cyclosporine A,Neoral,OL 27-400,Sandimmun,Sandimmun Neoral,Sandimmune,CsA Neoral,CsANeoral,CyA NOF,OL 27 400,OL 27400
D018432	Drug Resistance, Multiple	Simultaneous resistance to several structurally and functionally distinct drugs.	Drug Resistance, Extensively,Extensively Drug Resistance,Extensively-Drug Resistance,Multidrug Resistance,Multi-Drug Resistance,Extensively Drug Resistances,Extensively-Drug Resistances,Multiple Drug Resistance,Resistance, Extensively Drug,Resistance, Extensively-Drug,Resistance, Multiple Drug
D020168	ATP Binding Cassette Transporter, Subfamily B, Member 1	A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).	ATP-Dependent Translocase ABCB1,MDR1 Protein,MDR1B Protein,Multidrug Resistance Protein 1,P-Glycoprotein,P-Glycoprotein 1,ABCB1 Protein,ATP Binding Cassette Transporter, Sub-Family B, Member 1,ATP-Binding Cassette, Sub-Family B, Member 1,CD243 Antigen,PGY-1 Protein,1, P-Glycoprotein,ABCB1, ATP-Dependent Translocase,ATP Dependent Translocase ABCB1,Antigen, CD243,P Glycoprotein,P Glycoprotein 1,PGY 1 Protein,Protein, MDR1B,Translocase ABCB1, ATP-Dependent