scholarly journals Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells

2016 ◽  
Vol 14 (4) ◽  
pp. 226-239 ◽  
Author(s):  
Paul A. Johnston ◽  
Minh M. Nguyen ◽  
Javid A. Dar ◽  
Junkui Ai ◽  
Yujuan Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Nuclear Localization ◽  
High Throughput ◽  
High Content Screening ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Screening Assay ◽  
Castration Resistant

Down-Regulation of the Androgen Receptor by G-Quadruplex Ligands Sensitizes Castration-Resistant Prostate Cancer Cells to Enzalutamide

2018 ◽  
Vol 61 (19) ◽  
pp. 8625-8638 ◽  
Author(s):  
Martina Tassinari ◽  
Graziella Cimino-Reale ◽  
Matteo Nadai ◽  
Filippo Doria ◽  
Elena Butovskaya ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Down Regulation ◽  
Castration Resistant ◽  
G Quadruplex

scholarly journals PMA induces androgen receptor downregulation and cellular apoptosis in prostate cancer cells

2014 ◽  
Vol 53 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Momoe Itsumi ◽  
Masaki Shiota ◽  
Akira Yokomizo ◽  
Ario Takeuchi ◽  
Eiji Kashiwagi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Therapeutic Effects ◽  
Castration Resistant Prostate Cancer ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Cellular Apoptosis ◽  
Resistant Cells

Phorbol 12-myristate 13-acetate (PMA) induces cellular apoptosis in prostate cancer cells, the growth of which is governed by androgen/androgen receptor (AR) signaling, but the mechanism by which PMA exerts this effect remains unknown. Therefore, in this study, we investigated the mechanistic action of PMA in prostate cancer cells with regard to AR. We showed that PMA decreased E2F1 as well as AR expression in androgen-dependent prostate cancer LNCaP cells. Furthermore, PMA activated JNK and p53 signaling, resulting in the induction of cellular apoptosis. In LNCaP cells, androgen deprivation and a novel anti-androgen enzalutamide (MDV3100) augmented cellular apoptosis induced by PMA. Moreover, castration-resistant prostate cancer (CRPC) C4-2 cells were more sensitive to PMA compared with LNCaP cells and were sensitized to PMA by enzalutamide. Finally, the expression of PKC, E2F1, and AR was diminished in PMA-resistant cells, indicating that the gain of independence from PKC, E2F1, and AR functions leads to PMA resistance. In conclusion, PMA exerted its anti-cancer effects via the activation of pro-apoptotic JNK/p53 and inhibition of pro-proliferative E2F1/AR in prostate cancer cells including CRPC cells. The therapeutic effects of PMA were augmented by androgen deletion and enzalutamide in androgen-dependent prostate cancer cells, as well as by enzalutamide in castration-resistant cells. Taken together, PMA derivatives may be promising therapeutic agents for treating prostate cancer patients including CRPC patients.

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