Disease relevance of C14204

• In contrast, hydroxyflutamide (HF), an antiandrogen currently used to treat prostate cancer patients, only slightly inhibits LNCaP cell growth [1].
• Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia [2].
• The antiproliferative effect of hydroxyflutamide, without virilizing side-effects, suggests that it is worth exploring its possible employment together with antioestrogens in the treatment of breast cancer patients [3].
• Hydroxyflutamide (30 mg per day) for 5 days from day 11 to day 15 of gestation caused hypospadias in all male progeny [4].
• We investigated the effects of the proteasome inhibitors MG115 and PSI alone or in combination with different concentrations of the antiandrogen hydroxyflutamide on the cellular proliferation, apoptosis and viability of 10 prostatic adenocarcinoma cell cultures [5].

Psychiatry related information on C14204

• Inhibition of cell nuclear androgen receptor binding and copulation in male rats by an antiandrogen, Sch 16423 [6].

High impact information on C14204

• An antagonist ligand, hydroxyflutamide, blocked the NTD-LBD association within AR [7].
• Furthermore, we found this HER2/Neu --> MAP kinase --> AR-ARAs --> PSA pathway could not be blocked completely by hydroxyflutamide, an antiandrogen used in the treatment of prostate cancer [8].
• Coincubation with the testosterone receptor antagonist hydroxyflutamide (1 microM) blocked the testosterone-induced increase in TXA2 receptor density [9].
• Increasing expression of GSN enhances the AR activity in the presence of HF [10].
• There were significant differences between the wild-type and MRP1-overexpressing cells in efflux and accumulation of flutamide and hydroxyflutamide, its active metabolite [11].

Chemical compound and disease context of C14204

• In prostate cancer DU-145 cells, which were transiently transfected with CBP cDNA, hydroxyflutamide enhanced AR activity to a greater extent than bicalutamide in the presence of either wild-type or the mutated AR 730 val-->met [12].
• Comparison of the Pharmacological Effects of a Novel Selective Androgen Receptor Modulator (SARM), the 5alpha-Reductase Inhibitor Finasteride, and the Antiandrogen Hydroxyflutamide in Intact Rats: New Approach for Benign Prostate Hyperplasia (BPH) [13].
• Here we study the action of its active metabolite hydroxyflutamide on the oestradiol-induced growth of MCF-7 breast cancer cells [3].
• The purpose of our study was to evaluate the effects of 5 alpha-dihydrotestosterone (DHT) and hydroxyflutamide (HF), alone or in combination, on androgen receptor (AR) dynamics and on cellular growth in cultured breast cancer cells (EVSA-T) [14].
• Inhibitory effect of hydroxyflutamide plus tamoxifen on oestradiol-induced growth of MCF-7 breast cancer cells [3].

Biological context of C14204

• Interestingly, these compounds, in combination with hydroxyflutamide, further suppressed the Adiol-induced AR transactivation [15].
• The androgenic inhibition of cell proliferation was antagonized by the antiandrogens cyproterone acetate and hydroxyflutamide [16].
• In the absence of dihydrotestosterone, concentrations of 10 microM M2 or hydroxyflutamide promote AR binding to androgen response element DNA and activation of transcription [17].
• Dual blockade of androgen receptor function with the antiandrogen hydroxyflutamide and EGF receptor superfamily-mediated signal transduction with the anti-EGF receptor monoclonal antibody C225 and the anti-HER2 receptor monoclonal antibody Herceptin significantly enhanced growth inhibition of the MDA PCa 2a cells [18].
• The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation [19].

Anatomical context of C14204

• The anti-androgen hydroxyflutamide and androgens inhibit interleukin-6 production by an androgen-responsive human osteoblastic cell line [20].
• Finally, we demonstrated that hydroxyflutamide treatment of hFOB/AR-6 cells markedly inhibited the activation and binding of NF-kappaB (a known stimulator of IL-6 gene transcription) to its response element, thus providing a potential mechanism for its effect on IL-6 production by osteoblasts [20].
• After i.p. injection of hCG at 1600 h on Day 0, 92% of hydroxyflutamide-treated rats ovulated a mean of 8.3 +/- 1.2 oocytes compared to 100% of controls, which ovulated 7.3 +/- 0.4 oocytes per rat: these groups were not significantly different from each other, nor from control rats that received no hCG [21].
• Of surprise was the finding of an average DHT/HF index in 5 different nonprostate tissues, including breast, uterus, colon, kidney, and thyroid, that was similar to the index found in prostates [22].
• In addition, the nonsteroidal antiandrogen hydroxyflutamide (HO-F) does not influence primary epithelial cell proliferation in this concentration range [23].

Associations of C14204 with other chemical compounds

• Using mammalian two-hybrid assay, we report that antiandrogens, hydroxyflutamide, bicalutamide (casodex), cyproterone acetate, and RU58841, and other compounds such as genistein and RU486, can promote the interaction between AR and its coactivator, ARA70, in a dose-dependent manner [24].
• Functional analyses additionally demonstrate that GSN enhances AR activity in the presence of either androgen or HF [10].
• Although the AR-GFP bound to such antiandrogens as hydroxyflutamide or bicalutamide translocated to the nucleus, they homogeneously spread throughout the nucleus without producing any fluorescence foci [25].
• Certain antihormones, cyproterone acetate and RU486, promote ARE binding, but a pure antiandrogen, hydroxyflutamide, inhibits AR binding to ARE DNA [26].
• Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide [17].

Gene context of C14204

• Activation of mitogen-activated protein kinase pathway by the antiandrogen hydroxyflutamide in androgen receptor-negative prostate cancer cells [27].
• RESULTS: Fluorescence microscopy showed a distinct increase in immunostaining intensity in the nuclear interior after androgen treatment but no change in the subcellular distribution of Akt when the cells were pretreated with hydroxyflutamide (HF) or LY294002 [28].
• In the presence of OSM, hydroxyflutamide behaved as an AR agonist [29].
• Agonistic effect of the nonsteroidal antiandrogen hydroxyflutamide was strongly potentiated in prostate cells transfected with CBP cDNA [30].
• The agonistic activities of CPA- and hydroxyflutamide-occupied T877A-AR were hardly affected by N-CoR, whereas TIF2 strongly enhanced their activities [31].

Analytical, diagnostic and therapeutic context of C14204

• In two sublines of LNCaP cells that contain the mutated AR 877 thr-->ala and overexpressed CBP, increase in AR activity was observed after treatment with hydroxyflutamide but not with bicalutamide [12].
• The antisteroidal compounds, mifepristone (RU486) and hydroxyflutamide, were also found to inhibit specifically the P4- and DHT-mediated increase in ADAMTS-1 mRNA and protein expression levels in these primary cell cultures in a concentration-dependent manner, respectively [32].
• Muscle weights were also compared in animals receiving bilateral denervation of the BC/LA at the time of T and hFl capsule implantation and gonadectomy; local testosterone treatment failed to affect BC/LA weights in these denervated muscles [33].
• Just before the last dose and 15 times during the subsequent 24 h, blood samples were obtained for the determination of plasma hydroxyflutamide (the active metabolite of flutamide) levels by high-performance liquid chromatography [34].
• To test maintenance of copulatory behavior, T-filled capsules were implanted at the time of castration and rats received daily injections of either 0, 1, 5, 15 or 30 mg Sch 16423 [6].

References