Screening for androgen receptor activities in 253 industrial chemicals by in vitro reporter gene assays using AR-EcoScreenTM cells

Araki, Naoto; Ohno, Ken; Nakai, Makoto; Takeyoshi, Masahiro; Iida, Mitsuru

doi:10.1016/j.tiv.2005.04.009

Cited by 51 publications

(54 citation statements)

References 21 publications

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“…CHO data from literature: The data in the training set is comprised of experimental AR antagonism data from 15 publications [2][3][4]37,[39][40][41][42][43][44][45][46][47][48][49]. The data represents a wide range of chemical structures and various functions and covers natural hormones, synthetic hormones and drugs, pesticides, Polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), plasticizers and plastic additives, food additives and cosmetics, antioxidants, plant compounds, roast mutagens and various industrial chemicals.…”

Section: Data For Qsar Modelingmentioning

confidence: 99%

“…In addition, discrepancies in AR antagonism between cells may be due to chemical specific capacity for agonism and Luciferase inhibition [3,45,[56][57][58]. AR agonists are very rare among industrial and environmental chemicals (2/502 =0.5%) [2,3,39,43,44,47], but may be rather related to the steroid structure [3,35].…”

Section: Comparison Of Ar Antagonism Data Between Assays Based On Difmentioning

confidence: 99%

“…AR agonists are very rare among industrial and environmental chemicals (2/502 =0.5%) [2,3,39,43,44,47], but may be rather related to the steroid structure [3,35].…”

Section: Comparison Of Ar Antagonism Data Between Assays Based On Difmentioning

confidence: 99%

“…pesticides, industrial chemicals and drugs [1][2][3][4]. In vitro data for AR antagonism may be used for priority setting for further studies, e.g.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

QSAR Model for Androgen Receptor Antagonism - Data from CHO Cell Reporter Gene Assays

Jensen

Nikolov

Dreisig

et al. 2013

J Steroids Horm Sci

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Section: Data For Qsar Modelingmentioning

confidence: 99%

Section: Comparison Of Ar Antagonism Data Between Assays Based On Difmentioning

confidence: 99%

“…AR agonists are very rare among industrial and environmental chemicals (2/502 =0.5%) [2,3,39,43,44,47], but may be rather related to the steroid structure [3,35].…”

Section: Comparison Of Ar Antagonism Data Between Assays Based On Difmentioning

confidence: 99%

“…pesticides, industrial chemicals and drugs [1][2][3][4]. In vitro data for AR antagonism may be used for priority setting for further studies, e.g.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

QSAR Model for Androgen Receptor Antagonism - Data from CHO Cell Reporter Gene Assays

Jensen

Nikolov

Dreisig

et al. 2013

J Steroids Horm Sci

View full text Add to dashboard Cite

“…In vitro screenings have been based on ligand-binding assays, reporter gene assays, or conformational changes induced by the compound (19)(20)(21)(22)(23)(24)(25)(26). In vivo screens, directly observing effects on androgen-regulated tissues in mice or rats, and in silico screens, combining biologic data with computational methods, have also been used (27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of MEL-3, a Novel AR Antagonist That Suppresses Prostate Cancer Cell Growth

Helsen

Marchand

Chaltin

et al. 2012

Molecular Cancer Therapeutics

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Antiandrogens are an important component of prostate cancer therapy as the androgen receptor (AR) is the key regulator of prostate cancer growth and survival. Current AR antagonists, such as bicalutamide and hydroxyflutamide, have a low affinity for the AR and as a result block AR signaling insufficiently. Moreover, many patients develop a resistance for bicalutamide or hydroxyflutamide during therapy or show a clinical improvement after withdrawal of the antiandrogen. New and more effective AR antagonists are needed to ensure follow-up of these patients. We therefore developed a screening system to identify novel AR antagonists from a collection of compounds. MEL-3 [8-(propan-2-yl)-5,6-dihydro-4H-pyrazino[3,2,1-jk]carbazole] was selected as potent inhibitor of the AR and was further characterized in vitro. On different prostate cancer cell lines MEL-3 displayed an improved therapeutic profile compared with bicalutamide. Not only cell growth was inhibited but also the expression of androgen-regulated genes: PSA and FKBP5. Prostate cancer is often associated with mutated ARs that respond to a broadened spectrum of ligands including the current antiandrogens used in the clinic, hydroxyflutamide and bicalutamide. The activity of two mutant receptors (AR T877A and AR W741C) was shown to be reduced in presence of MEL-3, providing evidence that MEL-3 can potentially be a follow-up treatment for bicalutamide-and hydroxyflutamide-resistant patients. The mechanism of action of MEL-3 on the molecular level was further explored by comparing the structure-activity relationship of different chemical derivatives of MEL-3 with the in silico docking of MEL-3 derivatives in the binding pocket of the AR.

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Androgens and androgenic activity in broiler manure assessed by means of chemical analyses and in vitro bioassays

Valdehíta

Fernández‐Cruz

González-Gullón

et al. 2016

Enviro Toxic and Chemistry

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The use of manure as an agricultural amendment is increasing the release of steroid hormones into the environment. Most research in this field has focused on estrogenic phenomena, with less attention paid to androgenic substances. The present study assessed androgenic activity in broiler manure using in vitro approaches based on cells stably transfected with androgen receptor. Leaching experiments were also performed to observe whether endocrine disruptors present in manure pass through a soil column and potentially reach groundwater. In parallel, an analytical chemistry method was used to determine the contribution of the most important natural androgens to androgenicity. Samplings were performed at 4 farms in 2 seasons. All but 2 samples showed androgen activity. In leakage experiments, however, no androgenic activity was detectable in leachates or in soils after leaching. According to the analytical results, androgenicity can be attributed mainly (but not completely) to androstenedione, and dihydrotestosterone. Similarly to the bioassays, chemical analysis did not reveal the presence of any androgen in leachates or soils. These results point to a rapid degradation of the substances responsible for androgenic activity in soils under the experimental conditions of the present study. However, the long-term effects associated with the constant and intensive application of manure to agricultural land require further attention. Environ Toxicol Chem 2017;36:1746-1754. © 2016 SETAC.

show abstract

Screening for androgen receptor activities in 253 industrial chemicals by in vitro reporter gene assays using AR-EcoScreenTM cells

Cited by 51 publications

References 21 publications

QSAR Model for Androgen Receptor Antagonism - Data from CHO Cell Reporter Gene Assays

QSAR Model for Androgen Receptor Antagonism - Data from CHO Cell Reporter Gene Assays

Identification and Characterization of MEL-3, a Novel AR Antagonist That Suppresses Prostate Cancer Cell Growth

Androgens and androgenic activity in broiler manure assessed by means of chemical analyses and in vitro bioassays

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