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GSE107438 25D3 and 1,25D3 target gene profiles in LNCaP
In this study, we investigated whole genome target gene profiles and intracellular behaviors of VDR after administration of 25D3 or 1,25D3 in prostate cancer LNCaP cells to elucidate the hormonal activity of 25D3. First, we confirmed that LNCaP cells possessed functional 25D3-VDR as well as 1,25D3-VDR signaling systems by qRT-PCR. By immunofluorescent examination of nuclear translocation, western blotting and most importantly, knockdown o f CYP27B1 and/or VDR after the introduction of the respective siRNA into these cells, we found that, just like 1,25D3, 10-7 M of 25D3, which is within its uppermost physiological concentr...
Source: GEO: Gene Expression Omnibus - December 1, 2017 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a.
Abstract Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocyste...
Source: European Journal of Pharmacology - July 10, 2017 Category: Drugs & Pharmacology Authors: Uchiyama N, Tanaka Y, Kawamoto T Tags: Eur J Pharmacol Source Type: research

Radiosensitization by the investigational NEDD8-activating enzyme inhibitor MLN4924 (pevonedistat) in hormone-resistant prostate cancer cells.
Authors: Wang X, Zhang W, Yan Z, Liang Y, Li L, Yu X, Feng Y, Fu S, Zhang Y, Zhao H, Yu J, Jeong LS, Guo X, Jia L Abstract Salvage radiotherapy (SRT) is the first-line treatment for prostate cancer patients with biochemical recurrence following radical prostatectomy, and new specific radiosensitizers are in urgent need to enhance SRT effect. MLN4924 (also known as Pevonedistat), a specific inhibitor of NEDD8-activating enzyme, has recently entered phase I/II clinical trials in several malignancies. By inhibiting cullin neddylation, MLN4924 inactivates Cullin-RING ligases (CRL), which have been validated as an attra...
Source: Oncotarget - May 27, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Cyclin D1 silencing suppresses tumorigenicity, impairs DNA double strand break repair and thus radiosensitizes androgenindependent prostate cancer cells to DNA damage.
Authors: Marampon F, Gravina GL, Ju X, Vetuschi A, Sferra R, Casimiro MC, Pompili S, Festuccia C, Colapietro A, Gaudio E, Di Cesare E, Tombolini V, Pestell RG Abstract Patients with hormone-resistant prostate cancer (PCa) have higher biochemical failure rates following radiation therapy (RT). Cyclin D1 deregulated expression in PCa is associated with a more aggressive disease: however its role in radioresistance has not been determined. Cyclin D1 levels in the androgen-independent PC3 and 22Rv1 PCa cells were stably inhibited by infecting with cyclin D1-shRNA. Tumorigenicity and radiosensitivity were investigated u...
Source: Oncotarget - December 26, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

AMPK in TRAIL Combination-induced Apoptosis Signal Transduction
Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men with limited treatment options for the hormone-resistant forms. Development of novel therapeutic options is critically needed to target advanced forms. Here we demonstrate that combinatorial treatment with the thiazolidinedione troglitazone (TZD) and TNF-related apoptosis-inducing ligand (TRAIL) can induce significant apoptosis in various PCa cells independent of androgen receptor status. Because TZD is known to activate AMP-activated protein kinase (AMPK), we determined whether AMPK is a molecular target mediating this apoptotic cascade by utiliz...
Source: Journal of Biological Chemistry - September 4, 2015 Category: Chemistry Authors: Santha, S., Viswakarma, N., Das, S., Rana, A., Rana, B. Tags: Cell Biology Source Type: research