SFRP1 induces a stem cell phenotype in prostate cancer cells.

Prostate cancer (PCa) ranks second in incidence and sixth in deaths globally. The treatment of patients with castration-resistant prostate cancer (CRPC) continues to be a significant clinical problem. Emerging evidence suggests that prostate cancer progression toward castration resistance is associated with paracrine signals from the stroma. SFRP1 is one of the extracellular proteins that modulate the WNT pathway, and it has been identified as a mediator of stromal epithelium communication. The WNT pathway is involved in processes such as cell proliferation, differentiation, cell anchoring, apoptosis, and cell cycle regulation as well as the regulation of stem cell populations in the prostatic epithelium. In the present study, we explored the role of exogenous SFRP1 on the stem cell phenotype in prostate cancer. The results reveal that cancer stem cell markers are significantly increased by exogenous SFRP1 treatments, as well as the downstream target genes of the Wnt/-catenin pathway. The pluripotent transcription factors SOX2, NANOG, and OCT4 were also up-regulated. Furthermore, SFRP1 promoted prostate cancer stem cell (PCSC) properties in vitro, including tumorsphere formation, migration, bicalutamide resistance, and decreased apoptosis. Taken together, our results indicate that SFRP1 participates in the paracrine signaling of epithelial cells, influencing them and positively regulating the stem cell phenotype through deregulation of the WNT/ß-catenin pathway, which could contribute to disease progression and therapeutic failure. This research increases our molecular understanding of how CRPC progresses, which could help us find new ways to diagnose and treat the disease.

Beneficial effects of an algal oil rich in ω-3 polyunsaturated fatty acids on locomotor function and D2 dopamine receptor in haloperidol-induced parkinsonism.

INTRODUCTION: Parkinson's disease (PD) is a chronic neurological disorder whose pathogenesis involves the loss of dopaminergic neurons and dopamine terminals, formation of Lewy bodies, and microgliosis. Its treatment includes dopamine-based drugs with limited results and adverse effects. Additionally, some neuroleptic drugs used for mental disorders produce side effects referred to as parkinsonism. Dietary interventions with ω-3 polyunsaturated fatty acids (ω-3 PUFA) have attracted attention since they play a key role in most of the processes associated with PD etiology. OBJECTIVE: The purpose of our work was to investigate the effects of an ω-3 PUFA rich algal oil on locomotive alterations induced by haloperidol and D2 receptor protein and gene expression in Wistar rats. METHODOLOGY: Pre- and co-supplementation of algal oil (300 mg of ω-3 FA/kg/day for six weeks) and haloperidol (1.5 mg/kg/day for two weeks) were evaluated. RESULTS: Haloperidol provoked locomotive alterations in the Open Field Test and a 43% diminution in D2 receptor in brain membranes; in pre-supplemented rats a 93% increase in D2 receptor protein expression and a partial maintenance of locomotory performance were observed, while in co-supplemented rats D2 receptor protein expression was maintained as in control rats, although locomotive behavior was found diminished as in haloperidol rats. CONCLUSIONS: These results confirm the beneficial effects of ω-3 PUFA over locomotory alterations and as neuroprotective and neurorestorative compounds and demonstrates a stimulatory action on D2 receptor presence, as a mechanism by which these fatty acids participate in brain health.

Inhibition of Stearoyl-CoA Desaturase by Sterculic Oil Reduces Proliferation and Induces Apoptosis in Prostate Cancer Cell Lines.

Prostate cancer (PCa) is a common type of cancer affecting male population. PCa treatments have side effects and are temporarily effective, so new therapeutic options are being investigated. Due to the high demand of energy for cell proliferation, an increase in the expression and activity of lipogenic enzymes such as the stearoyl-CoA desaturase (SCD) have been observed in PCa. Sterculic acid, contained in the seed's oil of Malvales, is a natural inhibitor of SCD. The objective of our investigation was to evaluate the effects of sterculic oil (SO) from Sterculia apetala seeds on proliferation, cell cycle and apoptosis in prostate cancer cells. SO was administered to PC3 and LNCaP cells, and to prostate normal cells; cell viability, cell cycle, apoptosis, SCD gene and protein expression and enzymatic activity were analyzed. SO administration (4 mM sterculic acid) diminished cell viability in LNCaP and PC3 cells, arrested cell cycle in G2 and promoted apoptosis. SO diminished SCD enzymatic activity with no effects on gene nor protein expression. Our results suggest that SO might offer benefits as an adjuvant in hormonal and chemotherapy prostate cancer treatments. This is the first study to analyze the effect of SO on cancer cells.

Prostate Cancer Spheroids: A Three-Dimensional Model for Studying Tumor Heterogeneity.

Prostate cancer is one of the main causes of cancer and the sixth cause of death among men worldwide. One of the major challenges in prostate cancer research is cell heterogeneity defined as the different genomic and phenotypic characteristics in each individual cell making more difficult to assess the proper prostate cancer diagnosis and therapy. Tumor 3D spatial arrangement allow a strong interaction between the different cellular lineages and components which modulate cell proliferation, differentiation, and morphology. Prostate cancer spheroids are a cellular model which is capable to mimic the mechanical tensions of tumor tissue, providing a more representative pathophysiological model than the use of conventional 2D culture. Here, we describe a protocol to develop a 3D model of spheroids using prostate cancer cell lines (LNCaP, PC3, VCaP) which can be used to improve research considering tumoral heterogeneity role in cancer development, prognosis, and therapy.

Cell-Internalization SELEX of RNA Aptamers as a Starting Point for Prostate Cancer Research.

In the treatment of cancer, over the last decade different drugs delivery systems have been developed to increase therapeutic specificity to improve drug's efficacy, and safety by increasing bioavailability. Among these systems, small nucleic acid molecules with a three-dimensional structure, known as aptamers, have shown several advantages. Several approaches to design aptamers require modifications from starting libraries of DNA sequences. Here, we describe cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment), a sophisticated technique based on RNA aptamers as a starting point, that enables design functional aptamers as drug-delivery tools. This variation of the original SELEX technique using RNA aptamers instead DNA aptamers allows to obtain aptamers that are internalized in prostate cancer cells using as a starting point an RNA aptamer library with 76 nucleotides. The major advantage of this technique is that modifications are not required in the initial library, as initial T7 transcription promoter or 2'F nucleotides before sequencing.