Track topics on Twitter Track topics that are important to you
RU486 (Mifepristone) has been known as antiprogesterone and antiglucocorticoid agent. RU486 is also used for treatment of several cancers, such as breast, ovarian, prostate, and glaucoma. Here, we investigated the effect of RU486 on TRAIL-induced apoptosis in human renal carcinoma Caki cells. Low dose of RU486 (30-50 μM) alone had no effect on apoptosis, but RU486 markedly sensitized Caki cells to TRAIL-induced apoptosis. We found that up-regulation of death receptor 5 (DR5; receptor for TRAIL ligand), and down-regulation of Bcl-2 and c-FLIP (caspase regulator) contributes to RU-486 induced TRAIL sensitization. Down-regulation of DR5 by siRNA also blocked RU486 induced TRAIL sensitization. Furthermore, overexpression of Bcl-1 or c-FLIP(L) inhibited the cell death induced by the combined treatment with RU486 and TRAIL. RU486 increased DR5 expression at the transcriptional levels through induction of CHOP expression. By contrast, RU486 did not sensitize normal human mesangial cells to TRAIL-mediated apoptosis. Effect of RU486 on TRAIL-induced cancer cell apoptosis was independent of glucocorticoid receptor and progesterone receptor. Taken together, RU486 enhances TRAIL-mediated apoptosis through down-regulation of Bcl-2 and c-FLIP(L) as well as CHOP-mediated DR5 up-regulation.
Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, 704-701, South Korea.
This article was published in the following journal.
Name: Journal of molecular medicine (Berlin, Germany)
Breast cancer cells generally develop resistance to TNF-Related Apoptosis-Inducing Ligand (TRAIL) and, therefore, assistance from sensitizers is required. In our study, we have demonstrated that Splee...
Under conditions of periodic exposures to anxiogenic stress, intensifi cation of LPO in the brain cortex is a glucocorticoid-dependent process. Glucocorticoid receptor antagonist RU38486 prevented inc...
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gast...
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has potent antitumor effects in glioma cell lines but has shown little clinical benefit for patients. We investigated whether the widely...
The Notch1 signaling pathway contributes to tumorigenesis by influencing differentiation, proliferation and apoptosis. Here, we demonstrate that inhibition of the Notch1 signaling pathway sensitizes g...
The purpose of this study is to explore whether the GLP-1 receptor agonist exenatide, may prevent glucocorticoid-induced glucometabolic abnormalities and beta-cell dysfunction in healthy s...
The purpose of this study is to assess the effects of reducing the activity of endogenous glucocorticoid in patients with low-grade cortisol excess
Osteoporosis is a condition in which the amount of bone is reduced, the bones are weak, and there is an increased risk for fractures. Glucocorticoids (such as prednisone) are prescribed t...
Chemoradiotherapy has become the standard of care for women with locally advanced cervical cancer. The available data support a 30 to 50% reduction in the risk of death from cervical cance...
The dopamine agonists, pramipexole (Mirapex) and ropinirole (Requip), are drugs that are used to treat symptoms of Parkinson's disease. However, these drugs can induce bothersome leg swell...
A member of the TNF receptor family that was initially identified as a DEXAMETHASONE-induced protein from a T-CELL line. It may play a role in regulating APOPTOSIS and modulating immune response by T-lymphocytes. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary CUSHING SYNDROME.
A widely expressed member of the TNF receptor-associated family that may play a role in neuronal development and EMBRYOGENESIS. Although TNF receptor-associated factor 4 does not strongly associate with TUMOR NECROSIS FACTOR RECEPTORS it may be a signaling partner with the GLUCOCORTICOID-INDUCED TNFR-RELATED PROTEIN that plays a role in the activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES and NF-KAPPA B.
An orphan nuclear receptor that is closely related to members of the thyroid-steroid receptor gene family. It was originally indentified in NERVE CELLS and may play a role in mediation of NERVE GROWTH FACTOR-induced CELL DIFFERENTIATION. However, several other functions have been attributed to this protein including the positive and negative regulation of APOPTOSIS.
Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.
Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...