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Inhibition of FAS/FAS-ligand does not block chemotherapy-induced apoptosis in drug sensitive and resistant cells. 1999

D S Richardson, and P D Allen, and S M Kelsey, and A C Newland
Department of Haematology, St. Bartholomew's and Royal London School of Medicine, United Kingdom. d.s.richardson@mds.qmw.ac.uk

It has been suggested that one means by which chemotherapeutic agents exert their effect on leukaemic cells, is via autocrine induction of fas-ligand which then binds to fas (CD95), activates the caspase pathway and results ultimately in apoptotic death. In order to test this hypothesis, we have treated leukaemic cell lines with various chemotherapeutic agents (idarubicin, etoposide, fludarabine and 2-CdA) with and without pre-treatment with fas (ZB4) and fas-ligand (NOK-1) blocking monoclonal antibodies. Cell cycle analysis and quantitation of apoptosis were performed by flow cytometry following propidium iodide staining. HL-60 cells were found to be sensitive to the induction of apoptosis with all drugs tested but were highly resistant to treatment with a fas-ligating antibody (CH11). Apoptosis was neither inhibited in parental CEM cells nor their mdr-expressing drug resistant counterpart, CEM/VLB100 by pre-treatment with either ZB4 or NOK1. In addition, CEM/VLB100 were slightly more sensitive to treatment with CH11 (100 ng/ml) than parental CEM cells (% age apoptosis = 30.35 and 23.675, p = 0.024) and at least as sensitive to recombinant fas-ligand (50 ng/ml) (% age apoptosis = 26.6 and 20.2, p = NS). We conclude that it is unlikely that fas/fas-ligand interactions play a significant role in the induction of apoptosis by these chemotherapeutic agents in the leukaemic cell lines tested.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D005047 Etoposide A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Demethyl Epipodophyllotoxin Ethylidine Glucoside,Celltop,Eposide,Eposin,Eto-GRY,Etomedac,Etopos,Etoposide Pierre Fabre,Etoposide Teva,Etoposide, (5S)-Isomer,Etoposide, (5a alpha)-Isomer,Etoposide, (5a alpha,9 alpha)-Isomer,Etoposide, alpha-D-Glucopyranosyl Isomer,Etoposido Ferrer Farma,Exitop,Lastet,NSC-141540,Onkoposid,Riboposid,Toposar,VP 16-213,VP-16,Vepesid,Vépéside-Sandoz,Eto GRY,Etoposide, alpha D Glucopyranosyl Isomer,NSC 141540,NSC141540,Teva, Etoposide,VP 16,VP 16 213,VP 16213,VP16,Vépéside Sandoz,alpha-D-Glucopyranosyl Isomer Etoposide
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
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
D014740 Vidarabine A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus. Adenine Arabinoside,Ara-A,Arabinofuranosyladenine,Arabinosyladenine,9-beta-Arabinofuranosyladenine,9-beta-D-Arabinofuranosyladenine,Ara A,Vira-A,alpha-Ara A,alpha-D-Arabinofuranosyladenine,beta-Ara A,9 beta Arabinofuranosyladenine,9 beta D Arabinofuranosyladenine,Arabinoside, Adenine,Vira A,ViraA,alpha Ara A,alpha D Arabinofuranosyladenine,beta Ara A
D014747 Vinblastine Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.) Vincaleukoblastine,Cellblastin,Lemblastine,Velban,Velbe,Vinblastin Hexal,Vinblastina Lilly,Vinblastine Sulfate,Vinblastinsulfat-Gry,Sulfate, Vinblastine

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