Human malignant cell death by apoptosis-inducing nucleosides from the decidua derived CD57(+)HLA-DR(bright) natural suppressor cell line.
The CD57(+)HLA-DR(bright) natural suppressor (57.DR-NS) cell line derived from human decidual tissue mediated apoptosis of human leukemia Molt4 and carcinoma BeWo/GCIY cells but not human fibroblast WI-38 cells, and apoptosis-inducing nucleosides (AINs) appeared to be involved. Six AINs were released into 57.DR-NS cell culture media and were isolated by the combination of physicochemical procedures of C18 preparative column, thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC). Subsequently, we demonstrated that AINs could induce apoptosis in the human malignant Molt4/BeWo/GCIY cell line but not human normal WI-38 fibroblasts. Apoptosis was characterized by DNA strand breaks and activation of the caspase cascade, especially caspase-3. The administration of AINs into GCIY tumor bearing SCID mice culminated in suppression of tumor growth due to apoptosis of tumor cells.
Mori
Tsuneatsu
T
Department of Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan. ts-mori@ims.u-tokyo.ac.jp
Guo
Maowu
M
Li
Xiang
X
Mori
Etsuko
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018959:CD57 Antigens / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009705:Nucleosides / Q000494:pharmacology; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018959:CD57 Antigens; D006684:HLA-DR Antigens; D009705:Nucleosides; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases