Human T cell leukemia cell death by apoptosis-inducing nucleosides from CD57(+) HLA-DR(bright) natural suppressor cell line.
Apoptosis-inducing nucleosides (AINs) released from CD57( +) HLA-DR(bright) natural suppressor (57.DR-NS) cell line, derived from human decidual tissue, were isolated from 57.DR-NS cell culture supernatant by the combination of thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Apoptotic cell death was strongly induced in human T cell leukemia Molt4 cells treated with AINs, absolutely depending on DNA strand breaks, with activation of the caspase cascade, especially caspase-3. The administration of AINs to Molt4 tumor-bearing severe combined immunodeficiency (SCID) mice resulted in drastic suppression of tumor growth, with a decrease of tumor size and the appearance of apoptotic signals in tumor tissue. Thus, AINs are candidates for development as anticancer agents.
Mori
T
T
Department of Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-0071, Japan. ts-mori@ims.u-tokyo.ac. jp.
Li
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X
Mori
E
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Guo
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M
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018959:CD57 Antigens / Q000276:immunology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009705:Nucleosides / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018959:CD57 Antigens; D061945:Caspase Inhibitors; D004273:DNA, Neoplasm; D020536:Enzyme Activators; D006684:HLA-DR Antigens; D009705:Nucleosides; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases