Maowu Guo

Induction of apoptosis mediated by fas receptor and activation of caspase-3 in MRL-+/+ or MRL-lpr/lpr murine oocytes.

The molecular mechanisms leading to ovarian follicular atresia in the typical pathways of programmed cell death remain to be clarified. Here we have demonstrated that the apoptotic signalling pathway in MRL-+/+ (MRL/+) murine oocytes is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL-lpr/lpr (MRL/lpr) murine oocytes caused by insertion of the early transposable element (ETn) into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.

Human T Cell Leukemia Cell Death by Apoptosis‐inducing Nucleosides from CD57+ HLA‐DRbright Natural Suppressor Cell Line

Apoptosis‐inducing nucleosides (AINs) released from CD57+HLA‐DRbright 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.

Human malignant cell death by apoptosis-inducing nucleosides from the decidua derived CD57+HLA-DRbright 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.