Cytochrome C-dependent Fas-independent apoptotic pathway in HeLa cells induced by delta12-prostaglandin J2

Cyclopentenone prostaglandins (PGs) have antiproliferative activity on various tumor cell growth in vitro. Particularly, 9-deoxy-(9,12)-13,14-dihydro PGD2( delta12-PGJ2) was reported for its antineoplastic and apoptotic effects on various cancer cells, but its mechanism inducing apoptosis is still not clear. In this study, we have characterized apoptosis induced by delta12-PGJ2in HeLa cells. Treatment of delta12-PGJ2induced apoptosis as indicated by DNA fragmentation, chromatin condensation, and formation of apoptotic body. We also observed release of cytochrome c from mitochondria and activation of caspase cascade including caspase-3, -8, and -9. And the pan-caspase inhibitor z-Val-Ala-Asp (OMe) fluoromethyl-ketone (z-VAD-fmk) and Q-Val-Asp (OMe)-CH2-OPH (Q-VD (OMe)-OPH) prevented cell death induced by delta12-PGJ2 showing participation of caspases in this process. However, protein expression level of Bcl-2 family was not altered by delta12-PGJ2, seems to have no effect on HeLa cell apoptosis. And ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase 8 indicating that Fas receptor-ligand interaction was not involved in this pathway. Treatment of delta12-PGJ2 also leads to suppression of nuclear factor kappaB (NF-kappaB) as indicated by nuclear translocation of p65/RelA and c-Rel and its DNA binding ability analyzed by EMSA. Taken together, our results suggest that delta12-PGJ2-induced apoptosis in HeLa cell utilized caspase cascade without Fas receptor-ligand interaction and accompanied with NF-kappaB inactivation.

A Case of Malignant Lymphoma originated from uterine cervix / 대한산부인과학회잡지

The malignant lymphomas are neoplastic transformation of cells that reside predominantly in lymphoid tissues. The two major variants of malignant lymphoma are non-Hodgkin's lymphoma and Hodgkin's disease. Although both of these tumors infiltrate reticuloendothelial organs, their biologic and clinical behaviors suggest that they are probably not related. More than 90% of all cases of non-Hodgkin's lymphomas are of B-cell derivation. This observation is based upon the expression of B-lineage-restricted antigens as well as clonal rearrangements of immunoglobulin heavy and light chain genes. The malignant lymphoma localized in uterine cervix is rare and characteristically symptom-free expressed. We experienced a case of malignant lymphoma originated from uterine cervix, so we report with a brief of literature.

The Influence of Human Chorionic Gonadotropin and Human Placental Lactogen on Growth and Differentiation of Placental Trophoblast / 대한산부인과학회잡지

BACKGROUND: There are many factors that influence the differentiation and growth of trophoblasts. During differentiation of trophoblasts, two major hormones are secreted ; human chorionic gonadotropin (hCG) and human placental lactogen (hPL). These two hormones are secreted in a peculiar pattern during pregnancy and function of these hormones is not yet fully understood. Also, it is not known whether these hormones directly influence the differentiation and growth of trophoblasts. On the other hand, it is known that choriocarcinoma cells are undifferentiated, so they are unable to form syncytiotrophblasts. And many factors may be associated with this inhibitory potential. OBJECTIVE: The purpose of this study was to observe whether the hCG and hPL are associated with differentiation and growth of early placental trophoblasts and becoming malignant. METHOD: The hCG, hPL, IL-6 and insulin were added to cytotrophoblasts isolated from normal 8 to 10 gestational weeks' placental tissues by a degree of concentration, and observed the secreted hPL concentration and morphological change to syncytiotrophoblasts daily. And it was performed in Bewo cells in same manner. RESULT: The increased hPL secretion was noted in hCG, hPL, IL-6 and insulin were added normal trophoblasts and this may result from differentiation of cytotrophoblasts to syncytiotrophoblasts. Also, morphological changes to syncytiotrohoblasts was observed at the same time. But, Increased hPL secretion and syncytiotrophoblasts formation was not detected in Bewo cells. CONCLUSION: In this study, it seems that hCG, hPL, IL-6 and insulin had an influence on differentiation and growth of normal trophoblasts. On the other hand, no changes in hPL secretion and morphology at the choriocarcinoma cell line tells us that defects of differentiation in choriocarcinoma is due to abnormalities of the receptors on hCG and hPL or a differentiation associated gene, not a defect of these hormones themselves.

Influence of prostaglandin E2 and prostacyclin on vascular endothelial growth factor and basic fibroblast growth factor expression in cultured human trophoblast / 대한산부인과학회잡지

BACKGRUOND: Several angiogenic factors such as bFGF and VEGF have been shown angiogenesis of placenta. PGE2 and PGI2 may be important in successful establishment of pregnancy. OBJECTIVE: We studied to investigate whether PGE2 and PGI2 regulate expression of VEGF and bFGF gene in the cultured human trophoblast cells. METHODS: Human trophoblasts were isolated from the placenta of early gestation (6-12 weeks). Isolated trophoblasts were cultured in the different concentration of PGE2 and PGI2 and according to the different cultured time of PGE2 and PGI2, respectively. Total RNA was extracted and RT-PCR was performed. RESULT: Expression of bFGF was increased in 10-7M and 10-6M of PGE2 and was always increased in the all different concentration of PGI2. Four isoforms (VEGF121, VEGF165, VEGF189, VEGF206) were always expressed in the all different PGE2 and PGI2 concentration compared to the control group. However, there was no significant difference in the all different PGE2 and PGI2 concentration. In both PGE2 and PGI2 treatment group, expression of bFGF was decreased at 60 min compared to the control group and was gradually increased in time-dependent pattern. At 180 min, its expression was similar to the control group. CONCLUSION: Our data suggest that the expression of bFGF gene is influenced by cultured time and concentration of PGE2 and PGI2, although the expression of VEGF gene is not influenced.