The association between calcium channel blocker use and prostate cancer outcome

Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined

Lipid degradation promotes prostate cancer cell survival

Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential.</p

Targeting Androgen Receptor Action for Prostate Cancer Treatment: Does the Post-Receptor Level Provide Novel Opportunities?

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2014.01.02; Accepted: 2014.01.23; Published: 2014.06.01 The standard of care for patients who suffer from non-organ confined prostate cancer (CaP) is androgen deprivation therapy (ADT). ADT exploits the reliance of CaP cells on androgen receptor (AR) signaling throughout CaP progression from androgen-stimulated (AS) to castration-recurrent (CR) disease. AR is a member of the nuclear receptor family of ligand-activated transcription factors. Ligand-activated AR relocates from the cytoplasm to the nucleus, where it binds to Androgen Response Elements (AREs) to regulate transcription of target genes that control CaP cell behavior and progression. Current forms of ADT interfere at 2 levels along the AR signaling axis. At the pre-receptor level, ADT limits the availability of ligand for AR, while at the receptor level, ADT interrupts AR-ligand interactions. Both forms of ADT induce remission, but are not curative and, because of extraprostatic actions, are associated with severe side effects. Here, the potential of interference with the molecular regulation of AR-dependent transcription and the action of AR target genes, at the post receptor level, as the foundation for the developmen

Analyzing the Androgen Receptor Interactome in Prostate Cancer: Implications for Therapeutic Intervention

The androgen receptor (AR) is a member of the ligand-activated nuclear receptor family of transcription factors. AR&rsquo;s transactivation activity is turned on by the binding of androgens, the male sex steroid hormones. AR is critical for the development and maintenance of the male phenotype but has been recognized to also play an important role in human diseases. Most notably, AR is a major driver of prostate cancer (CaP) progression, which remains the second leading cause of cancer deaths in American men. Androgen deprivation therapies (ADTs) that interfere with interactions between AR and its activating androgen ligands have been the mainstay for treatment of metastatic CaP. Although ADTs are effective and induce remissions, eventually they fail, while the growth of the majority of ADT-resistant CaPs remains under AR&rsquo;s control. Alternative approaches to inhibit AR activity and bypass resistance to ADT are being sought, such as preventing the interaction between AR and its cofactors and coregulators that is needed to execute AR-dependent transcription. For such strategies to be efficient, the 3D conformation of AR complexes needs to be well-understood and AR-regulator interaction sites resolved. Here, we review current insights into these 3D structures and the protein interaction sites in AR transcriptional complexes. We focus on methods and technological approaches used to identify AR interactors and discuss challenges and limitations that need to be overcome for efficient therapeutic AR complex disruption

Androgen Signaling in Prostate Cancer

The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, progression to castration-resistant prostate cancer (CRPC) typically follows and is largely the result of restored androgen signaling. Efforts to understand the mechanisms behind CRPC have revealed new insights into dysregulated androgen signaling and intratumoral androgen synthesis, which has ultimately led to the development of several novel androgen receptor (AR)-directed therapies for CRPC. However, emergence of resistance to these newer agents has also galvanized new directions in investigations of prereceptor and postreceptor AR regulation. Here, we review our current understanding of AR signaling as it pertains to the biology and natural history of prostate cancer

Identification of an Androgen Response Element in Intron 8 of the Sterol Regulatory Element-binding Protein Cleavage-activating Protein Gene Allowing Direct Regulation by the Androgen Receptor

La calidad de los productos vegetales puede ser afectada por numerosas condiciones de precosecha. El uso de portainjertos en los productos hortícolas es una tecnología de cultivo innovadora que se viene empleando estratégicamente en Solanáceas y Cucurbitáceas para la búsqueda de resistencia a ciertas enfermedades e insectos del suelo, comportamiento frente a estrés, para aumentar el vigor de la planta o mejorar otros aspectos productivos (Gisbert et al., 2011; Moncada et al., 2013; Lopez- Marin et al., 2017). Los frutos de berenjena se hallan dentro de los 10 vegetales con mayor contenido de compuestos beneficiosos para la salud por sus propiedades anticancerígenas y antioxidantes dado que poseen gran cantidad de compuestos fenólicos. Los mismos se encuentran tanto en la pulpa como en la piel del fruto y están representados por ácido clorogénico y antocianinas, respectivamente. La berenjena se consume principalmente cuando alcanza el 80% de su tamaño final, aunque más recientemente se está incursionando en el consumo en estado más pequeño o baby. De acuerdo a esto el objetivo del presente trabajo fue analizar la diferencia de contenido y capacidad antioxidante de la piel y pulpa de frutos de berenjena provenientes de plantas control o injertadas en tres estadíos de crecimiento.Facultad de Ciencias Agrarias y Forestales (FCAF