scholarly journals Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, casodex

2000 ◽  
Vol 24 (3) ◽  
pp. 339-351 ◽  
Author(s):  
AS Waller ◽  
RM Sharrard ◽  
P Berthon ◽  
NJ Maitland
Keyword(s):  
Androgen Receptor ◽  
In Vitro Models ◽  
Human Prostate ◽  
Intracellular Targeting ◽  
Natural Ligand ◽  
Prostate Cells ◽  
Established Cell ◽  
Prostatic Epithelium ◽  
Prostate Epithelium

In vitro models of normal and malignant human prostate are currently limited to a few well established cell lines that, with a single exception (LNCaP), fail to express the androgen receptor (AR) - a common characteristic of prostatic epithelium grown in culture. To investigate the molecular mechanism of action of the non-steroidal antiandrogen Casodex (bicalutamide) against wild-type AR, we have established a transient AR expression model in non-tumorigenic prostate cells of both epithelial and mesenchymal origin. In this model, both dihydrotestosterone and Casodex can effectively transport the AR protein into the nucleus of prostate cells. Whereas the natural ligand, dihydrotestosterone, stabilises the receptor, the AR is rapidly degraded at a nuclear location when the transfected cells are treated with Casodex. In contrast, whereas the mutant AR in the LNCaP line is also degraded on Casodex treatment over the same time period, its intracellular targeting is defective.

scholarly journals Changes in the expression and functional activities of Myosin II isoforms in human hyperplastic prostate

2021 ◽  
Author(s):  
Weixiang He ◽  
Xiao Wang ◽  
Daxing Zhan ◽  
Mingzhou Li ◽  
Qian Wang ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Human Prostate ◽  
Common Disease ◽  
Organ Bath ◽  
Prostate Cell ◽  
Functional Activities ◽  
Prostate Cells ◽  
Induced Apoptosis ◽  
Muscle Myosin

Benign prostatic hyperplasia (BPH) is a common disease among aging males with the etiology remaining unclear. We recently found myosin II was abundantly expressed in rat and cultured human prostate cells with permissive roles in the dynamic and static components. This study aimed to explore the expression and functional activities of myosin II isoforms including smooth muscle myosin II (SMM II) and non-muscle myosin (NMM II) in the hyperplastic prostate. Human prostate cell lines and tissues from normal human and BPH patients were used. H&E, Masson’s trichrome, immunohistochemical staining, in vitro organ bath, RT-PCR and Western-blotting were performed. We further created cell models with NMM II isoforms silenced and proliferation, cycle, and apoptosis of prostate cells were determined by CCK-8 assay and flow cytometry. Hyperplastic prostate SM expressed more SM1 and LC17b isoforms compared to their alternatively spliced counterparts, favoring a slower more tonic-type contraction and greater force generation. For BPH group, blebbistatin (BLEB, a selective myosin II inhibitor), exhibited a stronger effect on relaxing phenylephrine (PE) pre-contracted prostate strips and inhibiting PE induced contraction. Additionally, NMMHC-A and NMMHC-B were upregulated in hyperplastic prostate with no change in NMMHC-C. Knockdown of NMMHC-A or NMMHC-B inhibited prostate cell proliferation and induced apoptosis, with no changes in cell cycle. Our novel data demonstrates that expression and functional activities of myosin II isoforms are altered in human hyperplastic prostate, suggesting a new pathological mechanism for BPH. Thus, the myosin II system may provide potential new therapeutic targets for BPH/lower urinary tract symptoms (LUTS).

307. The effect of oxytocin on cell growth and steroid production in normal human prostate cells in vitro

2005 ◽  
Vol 17 (9) ◽  
pp. 131
Author(s):  
K. J. Hogarth ◽  
K. King ◽  
H. D. Nicholson
Keyword(s):  
Cell Growth ◽  
Epithelial Cells ◽  
Stromal Cell ◽  
Human Prostate ◽  
Steroid Production ◽  
Cell Numbers ◽  
Prostate Cells ◽  
Normal Human ◽  
Oxytocin Antagonist

Oxytocin (OT) is present in reproductive tissues of male mammals including human prostate tissue. OT increases prostatic muscle tone and prostatic growth. OT is increased in benign prostatic hyperplasia (BPH), an androgen dependent condition that develops with age. Dihydrotestosterone (DHT) is the active hormone in the prostate and is converted from testosterone by the enzyme 5 a reductase. Conversion has been shown to be augmented in the presence of OT. The aim of this study was to investigate the effect of oxytocin on cell growth and steroid production in cultured normal human prostate cells. Normal human prostate stromal and epithelial cells (Clonetics) were cultured with OT, oxytocin antagonist (OTA) or oxytocin/oxytocin antagonist combination (10 ng/mL, 1 ng/mL or 0.1 ng/mL) in media containing 10 nmol of testosterone. Media was changed daily over the 5 day growth period and frozen. Cell proliferation assay was performed at harvest on day 5 to ascertain cell numbers. Media from days 1, 3 and 5 were extracted and radioimmunoassayed for testosterone and DHT. OT increased stromal cell number in a dose dependent manner (P < 0.001). Treatment with OT or OTA had no significant effect on epithelial cell numbers. In stromal cell media from Day 1, DHT concentrations were higher in cells treated with OT than control cells (P < 0.05). By Day 5 the concentration of DHT was low in all treatment groups except OT (10 ng/mL). No effect of OT or OTA was seen on DHT concentrations of media from epithelial cells. OT may increase cell growth in prostate stromal cells but not epithelial cells grown in vitro. This effect may be related to the conversion of testosterone to DHT and DHT to its metabolites. These results demonstrate that OT may play a role in the regulation of cell growth, steroid production and steroid metabolism in the human prostate.

BPA-induced prostatic hyperplasia in vitro is correlated to the unbalanced gene expression of AR and ER in the epithelium and stroma

2021 ◽  
pp. 074823372110429
Author(s):  
Kaiyue Wang ◽  
Dongyan Huang ◽  
Ping Zhou ◽  
Xin Su ◽  
Rongfu Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Gene Expressions ◽  
Proliferative Effect ◽  
M 10 ◽  
Prostate Epithelial Cells ◽  
Prostatic Epithelium ◽  
Underlying Mechanisms

As a typical environmental endocrine disruptor (EED), bisphenol A (BPA) can induce pathological hyperplasia of the prostatic epithelium and stroma. This study concentrates mainly on the effect and underlying mechanisms of BPA on prostatic hyperplasia, which is based on the culture of primary human prostate epithelial cells (HPEpiC) and human prostate fibroblasts (HPrF). In an effect to screen the optimal pro-survival BPA levels, HPEpiC and HPrF were, respectively, exposed to concentration gradients of BPA (10−12 M–10−4 M) solution diluted with two corresponding medium and incubated for 72 h at 37°C. CCK-8 assay showed that 10−9 M–10−5 M BPA could facilitate the proliferation of HPEpiC, while similar proliferative effect of HPrF only needed 10−11 M–10−7 M BPA. HPrF were more sensitive to BPA than HPEpiC. The qualification of PCNA gene expression measured using quantitative real-time polymerase chain reaction (qRT-PCR) also mirrored the BPA-induced cell proliferation. Additionally, our results considered that androgen receptor (AR), estrogen receptor (ERα, ERβ), and NFKB1 gene expressions exhibited up-regulation in HPEpiC treated with 10−9 M BPA for 72 h. However, in HPrF, the identical BPA treatment could activate ERα, ERβ, and NFKB1 gene expressions and down-regulated the expression of AR levels. It is further confirmed that low-dose BPA can indeed promote the proliferation of human prostate cells in vitro, and the mechanisms of BPA for prostatic epithelial and stromal hyperplasia may not be consistent.

scholarly journals Investigation of Equine In Vivo and In Vitro Derived Metabolites of the Selective Androgen Receptor Modulator (SARM) ACP-105 for Improved Doping Control

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 85
Author(s):  
Malin Nilsson Broberg ◽  
Heather Knych ◽  
Ulf Bondesson ◽  
Curt Pettersson ◽  
Scott Stanley ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
High Performance ◽  
Metabolite Profile ◽  
In Vitro Models ◽  
Doping Control ◽  
Cunninghamella Elegans ◽  
In Vivo Experiments ◽  
Receptor Modulator

Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-105 (2-chloro-4-[(3-endo)-3-hydroxy-3-methyl-8-azabicyclo[3.2.1]oct-8-yl]-3-methylbenzonitrile) in order to find analytical targets for doping control. Oral administration of ACP-105 was performed in horses, where blood and urine samples were collected over a time period of 96 h. The in vivo samples were compared with five in vitro incubation models encompassing Cunninghamella elegans, microsomes and S9 fractions of both human and equine origin. The analyses were performed using ultra-high performance liquid chromatography coupled to high resolution Q ExactiveTM OrbitrapTM mass spectrometry (UHPLC-HRMS). A total of 21 metabolites were tentatively identified from the in vivo experiments, of which several novel glucuronides were detected in plasma and urine. In hydrolyzed urine, hydroxylated metabolites dominated. The in vitro models yielded several biotransformation products, including a number of monohydroxylated metabolites matching the in vivo results. The suggested analytical target for equine doping control in plasma is a dihydroxylated metabolite with a net loss of two hydrogens. In urine, the suggested targets are two monohydroxylated metabolites after hydrolysis with β-glucuronidase, selected both due to prolongation of the detection time and the availability of reference material from the in vitro models.

scholarly journals Hormetic Dose Response of NaAsO2 on Cell Proliferation of Prostate Cells in Vitro: Implications for Prostate Cancer Initiation and Therapy

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581984337
Author(s):  
Johan Lundqvist ◽  
Erik Helmersson ◽  
Agneta Oskarsson
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Carcinoma Cells ◽  
Cancer Drug ◽  
Prostate Cells ◽  
Low Concentrations ◽  
High Concentrations ◽  
No Activation

Sodium meta-arsenite (NaAsO2) has been suggested to play a role both in initiation/progression of prostate cancer and as a future antiprostate cancer drug. We have studied the effects of NaAsO2 on cell proliferation of prostate cancer and noncancer cells, breast cancer cells, and adrenocortical carcinoma cells in vitro. Further, we have investigated the effect of NaAsO2 on the androgen receptor. We report that NaAsO2 alters the cell proliferation of prostate cells, in a hormetic manner, by increasing cell proliferation at low concentrations and decreasing the cell proliferation at high concentrations. No activation of the androgen receptor was detected. We conclude that NaAsO2 is able to increase cell proliferation of prostate cells in vitro at low concentrations, while it decreases cell viability at high concentrations. This novel finding has to be further addressed if NaAsO2 should be developed into an antiprostate cancer drug.

Effect of a standardized extract of red orange juice on proliferation of human prostate cells in vitro

Fitoterapia ◽  
2006 ◽  
Vol 77 (3) ◽  
pp. 151-155 ◽  
Author(s):  
Federica Vitali ◽  
Claudia Pennisi ◽  
Antonio Tomaino ◽  
Francesco Bonina ◽  
Anna De Pasquale ◽  
...  
Keyword(s):  
Orange Juice ◽  
Human Prostate ◽  
Prostate Cells

Glyoxalase 2 drives tumorigenesis in human prostate cells in a mechanism involving androgen receptor and p53-p21 axis

2017 ◽  
Vol 56 (9) ◽  
pp. 2112-2126 ◽  
Author(s):  
Cinzia Antognelli ◽  
Ivana Ferri ◽  
Guido Bellezza ◽  
Paola Siccu ◽  
Harold D. Love ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Human Prostate ◽  
Prostate Cells ◽  
Glyoxalase 2

scholarly journals Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

2009 ◽  
Vol 2009 ◽  
pp. 1-16 ◽  
Author(s):  
Rajasree Solipuram ◽  
Sowmya Koppula ◽  
Angela Hurst ◽  
Kinesha Harris ◽  
Srivatcha Naragoni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Lines ◽  
Cell Biology ◽  
Fold Increase ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Natural Ligand ◽  
Prostate Cells ◽  
Low Incidence

The low incidence of prostate cancer in Asians has been attributed to chemopreventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemopreventative properties of the Jamaican bush tea “Bizzy,” using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI50) of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the proapoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC50) of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.

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