• Journal of Life Science
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• v.19 no.7
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• pp.892-898
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• 2009

MIF is a progesterone analogue and is known as a potent progesterone antagonist. Although MIF has been known to inhibit prostate cancer cell growth, its molecular mechanisms are not yet clear. In the present study, when the cells were treated for 2-4 days with 5-40 $\mu$M of MIF, the growth and viability of LNCaP cells were significantly decreased in a dose- and time-dependent manner. When the cells, cultivated in a normal 2 mM calcium concentration medium, were treated with 15 $\mu$M MIF for 1 day, the intracellular calcium level increased by 26% compared to the control. Similar results were also found in cells located in the calcium-free reaction buffer, indicating that MIF induced the increase of intracellular Ca$^{2+}$ levels, regardless of the presence of calcium in the surrounding medium. In the cells treated with various concentrations of MIF, the intracellular calcium levels increased in a dose dependent manner. Cells treated with MIF revealed typical early apoptotic signs, i.e., chromosome condensation and nuclei fragmentation. In cells treated with 40 11M MIF, Bcl-2 decreased to 19% of the control. The expression of Bax increased to almost 2 fold of the control. These results demonstrated very clearly that MIF treatment blocks the expression of Bcl-2 but stimulates the expression of Bax. According to the results of the present investigation, the apoptotic mechanism of MIF is triggered by intracellular modulation.

• Proceedings of the Korean Society of Life Science Conference
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• 2001.09a
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• pp.112-112
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• 2001

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.04a
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• pp.25-44
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• 2007

The glucocorticoid receptor (GR) is an intracellular protein that is widely distributed throughout hippocampal and neocortical brain tissue. Mifepristone (RU486) is a potent GR antagonist that has also been shown to exhibit partial agonist-like effects. The precise location of the GR domain involved in the agonist-like activity of RU486 is unknown. Here, we examine this aspect of GR signaling by comparing human GR (hGR) construct with a Guyanese squirrel monkey GR (gsmGR) construct in which nuclear translocation and transactivation are known to be impaired. Using an objective translocation scoring method, we found that both hGR and gsmGR are translocated by RU486, and that nuclear translocation of hGR is significantly increased compared to gsmGR at 10 nM, 100 nM and 1000 nM RU486 in transiently transfected COS1 cells. While addition of RU486 to the cells transfected with hGR results in a 16-fold dose-dependent increase in transactivation compared to non-treated cells, no significant change in transactivation is observed with gsmGR at doses up to 100 nM RU486. Further experiments using six GR chimeras indicate that replacement of the hGR carboxyl-terminus of tau-1 transactivation domain (C-AF1, amino acids 132-428) with that from gsmGR diminishes hGR transactivation by RU486. These results demonstrate that RU486-induced transactivation of GR is determined in part by amino acids in the C-AF1 domain.

• Journal of Life Science
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• v.20 no.9
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• pp.1324-1331
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• 2010

Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.5
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• pp.649-656
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• 2015

The protective effect of zinc against cortisol-induced cell injury was examined in rainbow trout gill epithelial cells. Cells exposed to cortisol for 24 h showed increased leakage of lactate dehydrogenase (LDH) as well as decreased cell viability in a dose-dependent manner. Treatment with zinc ($100{\mu}M$ $ZnSO_4$) reduced the severity of both LDH release and cell death as well as protected cells against cortisol-induced caspase-3 activation, indicating reduction of apoptosis. Cortisol-induced cell death, leakage of LDH, and caspase-3 activation were blocked by the glucocorticoid receptor antagonist Mifepristone (RU-486), suggesting that cell injury was cortisol-dependent. In addition, we studied the effect of zinc on the expression of antioxidant genes such as metallothionein A (MTA), metallothionein B (MTB), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) during cortisol-induced cell injury. MTA, MTB, GST, and G6PD mRNA levels increased after treatment with zinc or cortisol, separately or in combination. Higher mRNA levels of MTA, MTB, GST, and G6PD were detected when cells were treated with $100{\mu}M$ $ZnSO_4$ and $1{\mu}M$ cortisol in combination at the same time compared to treatment with zinc or cortisol separately. Cells treated with zinc showed increased intracellular free zinc concentrations, and this response was significantly enhanced in cells treated with cortisol and zinc. In conclusion, zinc treatment inhibited cortisol-induced cytotoxicity and apoptosis through indirect antioxidant action.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.4
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• pp.160-174
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• 2007

Purpose: The purpose of this study was to investigate about missed abortion pathophysiology, diagnosis, medical treatment and to research the trend of the study related to missed abortion. Methods: We referred a PubMed site by using search word of "missed abortion"(Limits: 3 Year, only items with abstracts, Human). Results: 37 journals with 49 papers were searched. Conclusion: 1. The study of missed abortion pathophysiology was the following. The first was that important pathologies such as molar pregnancy and placental trophoblastic disease can be diagnosed by routine histopathologic analysis of product of conception following first-trimester spontaneous miscarriages. The second was that coelomic fluid leptin concentration in missed abortion is higher than in normal. The third was that adenosine deaminae activity in serum and placenta of patients with anembryonic pregnancies and missed abortions was low. The forth was that Leptotrichia amnionii sp. nov. was the etiopathogenetic factor in missed abortion. 2. Transvaginal ultrasound assessment of irregular vaginal bleeding is effective in diagonosis of missed abortion. 3. There were medical therapy with misoprostol, mifepristone or anti progesterone for missed abortion. Misoprostol was administrated oral(sublingual) and vaginal.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.2
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• pp.48-61
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• 2021

Objectives: This study was aimed to review the effect of acupuncture on endometriosis related pain in patients. Methods: Researchers searched data through 6 online databases up to November 2020. The data was limited to randomized controlled trial studies on endometriosis patients diagnosed with laparoscopy. Results: 7 Randomized controlled trials were included in this study. All of studies were published in Chinese, in China. Intervention of treatment group were composed of simple acupuncture and electroacupuncture. Intervention of control group were made up with mifepristone, herbal medicine and acupuncture. Outcome measurements were effective rate, serum Cancer antigen-125 (CA-125), Visual analogue scale (VAS)/pain score, and recurrence rate in 1 year. In all outcome measurements, treatment group were more effective than control group and it was statistically significant. Conclusions: Acupuncture therapy is effective in decreasing endometriosis related pain and preventing recurrence. However, because endometriosis is easy to recur, additional long-term research is needed.

• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.668-677
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• 2017

Embryo implantation is the crucial step for a successful pregnancy. Diverse factors, including adhesion molecules, growth factors, and cytokines are important for embryo implantation through improving endometrial receptivity. Benzoic acid (BA), a component of various plants, has been shown to have antifungal and antioxidant effects. However, the effect of BA on embryo implantation remains unknown. Here, we showed the contribution of BA for the enhancement of endometrial receptivity through the leukemia inhibitory factor (LIF)-dependent increase of integrin ${\alpha}V$, ${\beta}3$, and ${\beta}5$ expression. Furthermore, in vivo study using a mifepristone-induced implantation failure model showed that BA definitely improves the numbers of implantation embryos. Taken together, we suggest that BA has a novel function for embryo implantation through the up-regulation of LIF-mediated integrins, and may be a candidate for therapeutic medicine to increase the pregnancy rate.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.124-132
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• 2002

Daebangpung-tang(DBPT) is one of the prescriptions used for the treatment of rheumatoid arthritis(RA) in oriental medicine. The present study aimed to examine the analgesic effect of DBPT on a rat model of CFA-induced arthritis, which is not identical to human auto-immune arthritis although it does have many features in common with RA, and the relation between DBPT-induced analgesia and steroid hormones. CFA-induced arthritis rat model used to test the effect of DBPT was chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least the next 18 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral injection of indomethacin produced temporary improvement of weight bearing. DBPT dissolved in water was orally administrated. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 4 hours. DBPT produce significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 3 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. The reduced stepping force was divided into three stages(10-30g, 30-50g, and 50-70g). All experiments was performed at 50-70g of stepping force, since both DBPT and indomethacin showed the most excellent analgesic effect at 50-70g of stepping force. DBPT produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner and showed analgesic effect on neuropathic pain as well. DBPT-induced analgesic effect could not be blocked by systemic injection of steroid antagonist mifepristone. The present study suggest 1) that DBPT produces a potent analgesic effect on the chronic knee arthritis pain model in the rat and 2) that steroids system does not mediate DBPT-induced analgesia.