ascorbic-acid and Choriocarcinoma
ascorbic-acid has been researched along with Choriocarcinoma* in 7 studies
Other Studies
7 other study(ies) available for ascorbic-acid and Choriocarcinoma
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Ascorbic acid uptaken by sodium-dependent vitamin C transporter 2 induces βhCG expression through Sp1 and TFAP2A transcription factors in human choriocarcinoma cells.
Vitamin C [ascorbic acid (AA)] is transported by sodium-dependent vitamin C transporters (SVCT) 1 and 2, and our previous studies show AA induces a dramatic production of steroid hormones in human choriocarcinoma cells. However, whether AA induces the production of placental polypeptide hormones remains unknown. Here we investigated the mechanisms governing AA-induced β-human chorionic gonadotropin (hCG) expression.. Frozen sections from human term placentas were used for immunostaining of SVCT, and βhCG mRNA expression and its production in primary human placental cytotrophoblasts and JEG-3 cells were examined by quantitative RT-PCR and ELISA, respectively. Knockdown of SVCT2, transcription factor activating enhancer-binding protein 2α (TFAP2A), or specificity protein-1 (Sp1) expression was achieved by retrovirus-mediated short hairpin RNA, and the transcriptional factors responsible for AA-induced βhCG expression was identified by reporter constructs.. Both SVCT1 and SVCT2 are expressed in human term placentas. SVCT2 is predominantly localized in the syncytial layer, whereas SVCT1 is predominantly distributed in the villous core. AA dramatically induces βhCG mRNA expression and its production in JEG-3 cells and primary human cytotrophoblasts, and knockdown of SVCT2 expression in JEG-3 cells significantly decreases AA-induced βhCG expression. Data from βhCG5 construct and its deletion mutants further indicate that AA induces βhCG5 transactivation through Sp1 and TFAP2A transcriptional factors, and silence of Sp1 and/or TFAP2A expression significantly decreased AA-induced βhCG5 reporter activity and βhCG expression as well.. The present study revealed the novel effects of AA on polypeptide hormone, βhCG, production and the potential mechanisms governing AA-induced βhCG expression, suggesting the potentially indispensable roles of AA in placental endocrine and pregnant maintenance. Topics: Adult; Ascorbic Acid; Blotting, Western; Cell Line, Tumor; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Cyclic AMP; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Genetic Vectors; Humans; Placenta; Plasmids; Pregnancy; Real-Time Polymerase Chain Reaction; Retroviridae; RNA, Messenger; RNA, Small Interfering; Sodium-Coupled Vitamin C Transporters; Sp1 Transcription Factor; Transcription Factor AP-2 | 2012 |
Effects of vitamins C and E, acetylsalicylic acid and heparin on fusion, beta-hCG and PP13 expression in BeWo cells.
Preeclampsia is one of the leading causes for maternal and fetal morbidity. Placental protein 13 (PP13) is a placenta specific protein and with its decreased maternal serum levels in the first trimester it is one of the most promising markers to predict the syndrome in early pregnancy. In clinical trials attempts to prevent preeclampsia have already been made using low-dose aspirin, low-molecular-weight heparin, and antioxidants such as vitamins C and E. Here we investigated the effect of these agents on PP13 and beta-hCG levels using choriocarcinoma cell lines as surrogates for primary villous trophoblast. Five different cell lines were triggered with forskolin and cultured for 48 h. Amongst the five tested cell lines BeWo cells showed the strongest increase in PP13 mRNA after forskolin treatment compared to controls. Hence these cells were used to investigate the effect of varying concentrations of vitamin C, acetylsalicylic acid (ASA), Trolox) and heparin on cell fusion and PP13 and beta-hCG levels. The response to vitamin C was a dose-dependent increase in protein expression, while the other drugs showed only modest effects. Since first trimester PP13 has been shown to be significantly decreased in women subsequently developing preeclampsia, this data might point to a beneficial effect of very early vitamin C treatment of such women already in the early first trimester of pregnancy. Topics: Antioxidants; Ascorbic Acid; Aspirin; Cell Fusion; Cell Line, Tumor; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Chorionic Villi; Colforsin; Drug Therapy, Combination; Female; Galectins; Gene Expression; Heparin; Humans; Pregnancy Proteins; RNA, Messenger; Trophoblasts; Vitamin E; Xenobiotics | 2010 |
Vitamin C enhances phagocytosis of necrotic trophoblasts by endothelial cells and protects the phagocytosing endothelial cells from activation.
Preeclampsia is a pregnancy-specific disease characterised by maternal hypertension that is preceded by endothelial cell activation and an inappropriate inflammatory response. The exact cause of preeclampsia is unclear but this disease is known to be induced by a placental factor and it is hypothesised that oxidative stress may also contribute to its pathogenesis. We have shown that dead trophoblasts shed from the placenta can be phagocytosed by endothelial cells and that phagocytosis of necrotic, but not apoptotic, trophoblasts leads to endothelial cells activation. Since phagocytosis may be accompanied by an oxidative burst which may lead to damage/activation of the phagocyte, in this study we have investigated whether the antioxidant vitamin C can protect endothelial cells that phagocytose necrotic trophoblasts from activation. We demonstrate that treatment of phagocytosing endothelial cells with vitamin C induced an increase in the phagocytosis of necrotic trophoblasts but that activation of the phagocytosing endothelial cells was prevented. Treatment of phagocytosing endothelial cells with vitamin C also prevented the increase in IL-6 secretion that normally accompanies phagocytosis of necrotic trophoblasts. Thus treatment of endothelial cells with vitamin C appears to modify both the phagocytosis of necrotic trophoblasts and the response of the endothelial cells to the necrotic trophoblastic material. Topics: Adult; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Choriocarcinoma; Endothelial Cells; Female; Humans; Interleukin-6; Necrosis; Phagocytosis; Pre-Eclampsia; Pregnancy; Trophoblasts; Umbilical Veins; Young Adult | 2009 |
Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells.
Reduced vitamin C [ascorbic acid (AA)], which is taken up into cells by sodium-dependent vitamin C transporter (SVCT) 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. To determine the steroidogenic effect of AA and the role of SVCT2 in AA-induced steroidogenesis, we tested the effects of AA treatment and SVCT2 knockdown on steroidogenesis in human choriocarcinoma cell lines. AA treatment of JEG-3, BeWo, and JAR cells for 48-h dose dependently increased progesterone and estradiol levels. In JEG-3 cells, AA increased the mRNA expression of P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase, key enzymes for steroidogenesis. Stable knockdown of SVCT2 in JEG-3 cells by retrovirally mediated RNA interference decreased the maximal velocity of AA uptake by approximately 50%, but apparent affinity values were not affected. SVCT2 knockdown in JEG-3 cells significantly suppressed the AA-induced mRNA expression of placental P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase. This suppression of the AA-induced mRNA expression of steroidogenic enzymes subsequently decreased progesterone and estradiol production. In addition, inhibition of MAPK kinase-ERK signaling, which is a major pathway for AA-regulated gene expression, failed to affect AA-induced steroidogenesis. Our observations indicate that SVCT2-mediated AA uptake into cells is necessary for AA-induced steroidogenesis in human choriocarcinoma cell, but MAPK kinase-ERK signaling is not involved in AA-induced steroidogenesis. Topics: 3-Hydroxysteroid Dehydrogenases; Aromatase; Ascorbic Acid; Cholesterol Side-Chain Cleavage Enzyme; Choriocarcinoma; Estradiol; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Mitogen-Activated Protein Kinase Kinases; Models, Biological; Organic Anion Transporters, Sodium-Dependent; Pregnancy; Progesterone; RNA, Messenger; RNA, Small Interfering; Sodium-Coupled Vitamin C Transporters; Steroids; Symporters; Tumor Cells, Cultured; Uterine Neoplasms | 2008 |
Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function.
We report here on the cloning and functional characterization of human SVCT2, a sodium-dependent vitamin C (ascorbate) transporter. The hSVCT2 cDNA obtained from a human placental choriocarcinoma cell cDNA library, codes for a protein of 650 amino acids with a predicted molecular mass of 70 kDa. At the level of amino acid sequence, the human SVCT2 exhibits 95% identity to its rat homolog. When functionally expressed in mammalian cells, hSVCT2 induces the transport of ascorbic acid. The transport process induced by hSVCT2 is Na(+)-dependent and is specific for ascorbate. The Michaelis-Menton constant (K(t)) for the transport of ascorbate in cDNA-transfected cells is 69 +/- 5 microM. The relationship between the cDNA-specific uptake rate of ascorbate and Na(+) concentration is sigmoidal with a Na(+):ascorbate stoichiometry of 2:1. Northern blot analysis shows that SVCT2-specific transcripts are present in heart, brain, placenta, and liver and is absent in lung and skeletal muscle. The size of the principal transcript is approximately 7.5 kb. Topics: Amino Acid Sequence; Animals; Ascorbic Acid; Base Sequence; Biological Transport; Cell Line; Choriocarcinoma; Cloning, Molecular; Female; Gene Library; Humans; Kinetics; Molecular Sequence Data; Organic Anion Transporters, Sodium-Dependent; Pregnancy; Proteins; Rats; Recombinant Proteins; Sodium; Sodium-Coupled Vitamin C Transporters; Substrate Specificity; Symporters; Transfection; Tumor Cells, Cultured; Uterine Neoplasms | 1999 |
Transport mechanisms for vitamin C in the JAR human placental choriocarcinoma cell line.
We investigated the transport pathways available for the uptake of vitamin C in the human placental choriocarcinoma cell line, JAR. These cells were found to possess the capacity to accumulate the vitamin when presented either in the oxidized form (dehydroascorbic acid) or in the reduced form (ascorbate). Dithiothreitol and 5,5'-dithiobis(2-nitrobenzoic acid) were used to maintain vitamin C as ascorbate and dehydroascorbic acid, respectively. The uptake of these two forms of vitamin C in JAR cells was found to occur by different mechanisms. The uptake of the dehydroascorbic acid was Na(+)-independent and was mediated by facilitative glucose transporters as evidenced from the inhibition of the uptake process by glucose. On the other hand, the uptake of ascorbate was Na(+)-dependent and was not sensitive to inhibition by glucose. Substitution of Na+ with other monovalent cations abolished the uptake of ascorbate completely. The uptake process was, however, not influenced by anions. Kinetic analysis indicated the presence of a single saturable transport system for ascorbate with a Michaelis-Menten constant of 22 +/- 1 microM. The dependence of the uptake rare of ascorbate on Na+ concentration exhibited sigmoidal kinetics, suggesting interaction of more than one Na+ ion with the transporter. The Hill coefficient for the Na+ interaction was 2, indicating that the Na(+)-dependent ascorbate transport is electrogenic. The Na(+)-dependent stimulation of ascorbate uptake was primarily due to an increase in the affinity of the transporter for ascorbate in the presence of Na+. It is concluded that the JAR placental trophoblast cell line expresses two different transport systems for vitamin C: one for the reduced form of the vitamin ascorbate; and the other for the oxidized form of the vitamin dehydroascorbic acid. Topics: Ascorbic Acid; Biological Transport; Carrier Proteins; Choriocarcinoma; Dithionitrobenzoic Acid; Dithiothreitol; Female; Humans; Placenta; Sodium; Tumor Cells, Cultured; Uterine Neoplasms | 1998 |
[Is the dissociation of the biological and immunological activity of luteinizing hormone in tumor patients--an artifact, factor of proliferation, isohormone, endogenous anahormone--the result of the effect of antigonadotropins or simple inactivation?].
Topics: Adenoma, Chromophobe; Ascorbic Acid; Breast Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Female; Hemagglutination Inhibition Tests; Humans; Immune Sera; Luteinizing Hormone; Menopause; Middle Aged; Pituitary Neoplasms; Pregnancy; Uterine Neoplasms | 1967 |