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.