TNF-induced apoptosis in multidrug resistant friend erythroleukemia is not influenced by the P-glycoprotein and glutathione status of the cell line.
The effects that TNF-alpha exerts on Friend erythroleukemia (FLC) and on one multidrug resistant variant (FLC-DXR) of the cell line were studied. Resistance to doxorubicin of FLC-DXR entails two mechanisms: overexpression of P-glycoprotein; and increased glutathione-related activities. Both these might also decrease the effects of the cytokine. Nonetheless, TNF caused even greater cytotoxicity and apoptosis, with no induction of differentiation markers, in FLC-DXR. In addition, TNF produced minor changes of the levels of reduced and oxidized glutathione in the cell lines, and its cytotoxic effects were not inluenced by agents that modify the cell glutathione content such as buthionine sulfoximine, ethacrynic acid, or N-acetyl cysteine. We can exclude that the mechanisms of drug resistance of FLC-DXR prevent the response to the cytokine.
Flugy
A
A
Facoltá di Medicina e Chirurgia, Universitá di Palermo, Italy.
Borsellino
N
N
D'Alessandro
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D005622:Friend murine leukemia virus; D005978:Glutathione / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D051379:Mice; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004232:Diuretics; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019328:Buthionine Sulfoximine; D004317:Doxorubicin; D007371:Interferon-gamma; D005978:Glutathione; D004976:Ethacrynic Acid; D000111:Acetylcysteine