Effects of apoptosis-inducing nucleosides released from CD57+HLA-DRbright natural suppressor cell line on human breast cancer cell death and growth.
The CD57+HLA-DRbright-natural suppressor (57.DR-NS) cell line induced apoptosis in estrogen-non-responsive human breast carcinoma MDA-MB-435 cells by apoptosis-inducing nucleosides (AINs) released into the cultures. We obtained six active AINs isolated by high performance liquid chromatography (HPLC) from 57.DR-NS cell cultures. Each AIN isolated from 57.DR-NS cell cultures induced apoptosis in MDA-MB-435 cells. We found the occurrence of DNA strand breaks followed by the activation of caspase-3 during AIN-induced apoptosis in MDA-MB-435 cells. The data obtained here indicated that 57.DR-NS cells could induce apoptosis in MDA-MB-435 cells mediated by AINs through DNA strand breaks and activation of caspase-3. Furthermore, the administration of AINs into MDA-MB-435 tumor-bearing SCID mice culminated in strong suppression of tumor growth with no change of body weight of experimental mice suggesting no side effects of AINs.
Guo
Maowu
M
Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan.
Jin
Aishun
A
Qi
Yunlong
Y
Mori
Etsuko
E
Mori
Tsuneatsu
T
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018959:CD57 Antigens / Q000096:biosynthesis*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D013997:Time Factors
D018959:CD57 Antigens; D006684:HLA-DR Antigens; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases