English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The management of hormone-refractory prostate cancer represents a major challenge in the therapy of this tumor, and identification of novel androgen receptor antagonists is needed to render treatment more effective. We analyzed the activity of two novel androgen receptor antagonists, ( S )- 11  and ( R )- 9 , in  in vitro  and  in vivo  experimental models of hormone-sensitive or castration-resistant prostate cancer (CRPC).  In vitro  experiments were performed on LNCaP, LNCaP-AR, LNCaP-Rbic and VCaP human prostate cancer cells. Cytotoxic activity was assessed by SRB and BrdU uptake, AR transactivation by luciferase reporter assay and PSA levels by Real Time RT-PCR and ELISA assays. Cell cycle progression-related markers were evaluated by western blot.  In vivo  experiments were performed on SCID mice xenografted with cells with different sensitivity to hormonal treatment. In hormone-sensitive LNCaP and LNCaP-AR cells, the latter expressing high androgen receptor levels, ( R )- 9  and ( S )- 11  exhibited a higher cytotoxic effect compared to that of the reference compound (( R )-bicalutamide), also in the presence of the synthetic androgen R1881. Furthermore, the cytotoxic effect produced by ( R )- 9  was higher than that of ( S )- 11  in the two hormone-resistant LNCaP-AR and VCaP cells. A significant reduction in PSA levels was observed after exposure to both molecules. Moreover, ( S )- 11  and ( R )- 9  inhibited DNA synthesis by blocking the androgen-induced increase in cyclin D1 protein levels.  In vivo  studies on the toxicological profile of ( R )- 9  did not reveal the presence of adverse events. Furthermore, ( R )- 9  inhibited tumor growth in various  in vivo  models, especially LNCaP-Rbic xenografts, representative of recurrent disease. Our  in vitro  results highlight the antitumor activity of the two novel molecules ( R )- 9  and ( S )- 11 , making them a potentially attractive option for the treatment of CRPC.

Effect of Small Molecules Modulating Androgen Receptor (SARMs) in Human Prostate Cancer Models