Bacterial RNA virus MS2 exposure increases the expression of cancer progression genes in the LNCaP prostate cancer cell line.

Bacteriophages effectively counteract diverse bacterial infections, and their ability to treat most types of cancer has been explored using phage engineering or phage-virus hybrid platforms. In the present study, it was demonstrated that the bacteriophage MS2 can affect the expression of genes associated with the proliferation and survival of LNCaP prostate epithelial cells. LNCaP cells were exposed to bacteriophage MS2 at a concentration of 1×107 plaque forming units/ml for 24-48 h. After exposure, various cellular parameters, including cell viability, morphology, and changes in gene expression, were examined. MS2 affected cell viability adversely, reducing viability by 25% in the first 4 h of treatment; however, cell viability recovered within 24-48 h. Similarly, the AKT, androgen receptor, integrin α5, integrin ß1, MAPK1, MAPK3, STAT3, and peroxisome proliferator-activated receptor-γ coactivator 1α genes, which are involved in various normal cellular processes and tumor progression, were significantly upregulated, whereas the expression levels of HSP90, ITGB5, ITGB3, HSP27, ITGAV, and PI3K genes were unchanged. Therefore, based on viability and gene expression changes, bacteriophage MS2 severely impaired LNCaP cells by reducing anchorage-dependent survival and androgen signaling. A caveolin-mediated endocytosis mechanism for MS2-mediated signaling in prostate cancer cells was proposed based on reports involving bacteriophages T4, M13, and MS2, and their interactions with LNCaP and PC3 cell lines.

Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line.

Wild-type or engineered bacteriophages have been reported as therapeutic agents in the treatment of several types of diseases, including cancer. They might be used either as naked phages or as carriers of antitumor molecules. Here, we evaluate the role of bacteriophages M13 and T4 in modulating the expression of genes related to cell adhesion, growth, and survival in the androgen-responsive LNCaP prostatic adenocarcinoma-derived epithelial cell line. LNCaP cells were exposed to either bacteriophage M13 or T4 at a concentration of 1 × 105 pfu/mL, 1 × 106 pfu/mL, and 1 × 107 pfu/mL for 24, 48, and 72 h. After exposure, cells were processed for general morphology, cell viability assay, and gene expression analyses. Neither M13 nor T4 exposure altered cellular morphology, but both decreased the MTT reduction capacity of LNCaP cells at different times of treatment. In addition, genes AKT, ITGA5, ITGB1, ITGB3, ITGB5, MAPK3, and PI3K were significantly up-regulated, whilst the genes AR, HSPB1, ITGAV, and PGC1A were down-regulated. Our results show that bacteriophage M13 and T4 interact with LNCaP cells and effectively promote gene expression changes related to anchorage-dependent survival and androgen signaling. In conclusion, phage therapy may increase the response of PCa treatment with PI3K/AKT pathway inhibitors.

Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer.

Prostate cancer (PCa) is the leading cause of cancer-associated mortality in men, and new biomarkers are still needed. The expression pattern and protein tissue localization of proteoglycans of the syndecan family (SDC 1-4) and syntenin-1 (SDCBP) were determined in normal and prostatic tumor tissue from two genetically engineered mouse models and human prostate tumors. Studies were validated using SDC 1-4 and SDCBP mRNA levels and patient survival data from The Cancer Genome Atlas and CamCAP databases. RNAseq showed increased expression of Sdc1 in Pb-Cre4/Ptenf/f mouse Pca and upregulation of Sdc3 expression and downregulation of Sdc2 and Sdc4 when compared to the normal prostatic tissue in Pb-Cre4/Trp53f/f-;Rb1f/f mouse tumors. These changes were confirmed by immunohistochemistry. In human PCa, SDC 1-4 and SDCBP immunostaining showed variable localization. Furthermore, Kaplan-Meier analysis showed that patients expressing SDC3 had shorter prostate-specific survival than those without SDC3 expression (log-rank test, p = 0.0047). Analysis of the MSKCC-derived expression showed that SDC1 and SDC3 overexpression is predictive of decreased biochemical recurrence-free survival (p = 0.0099 and p = 0.045, respectively), and SDC4 overexpression is predictive of increased biochemical recurrence-free survival (p = 0.035). SDC4 overexpression was associated with a better prognosis, while SDC1 and SDC3 were associated with more aggressive tumors and a worse prognosis.

Effect of concurrent training and supplementation with ß-hydroxy- ß-methylbutyirate (hmb) on the prostate: alterations in the androgen receptor and inflammation / Efecto del entrenamiento concomitante y suplementación con ß-hidroxi-ß-metilbutirato (hmb) en la próstata: alteraciones en el receptor de andrógenos y la inflamación

SUMMARY: Supplementation is a strategy to potentiate physical training through hypertrophy of skeletal muscles, but other tissues such as the prostate may also be affected. Changes in prostate size and function are associated with the behavior of individuals, but evidence for an association with supplementation is scarce. Therefore, the aim of our study was to evaluate the effect of b-hydroxy bmethylbutyrate (HMB) supplementation and concurrent training on the prostate. Wistar rats were divided randomly into four groups with 10 animals each: control group (C), supplemented group (S), training group (T), and supplemented plus training group (TS). The supplemented groups (S and TS) received 76 mg·kg/day of HMB and the concurrent training groups (T and TS) performed exercise three times per week for eight weeks. HMB increased body composition, total weight of the prostate, and altered the histology of prostatic compartments. The lateral prostate of animals in the supplemented group had an increase in mast cells per mm2 (28.0 ± 3.9) compared to the control and exercise group (6.1 ± 3.0; 2.3 ± 0.9) There was also an increase in inflammation in the stroma and lumen of the prostate, and increased expression of androgen receptor (AR) in the supplemented and trained supplemented group (79.8 ± 2.1; 76.8 ± 11.4) in relation to the trained group (61.5 ± 7.0). We concluded that HMB alters hormone receptors that induce morphological changes and inflammation, and animals in the concurrent training group had normal inflammatory and hormonal profiles, and favorable prostatic histology.

RESUMEN: La suplementación con β-hidroxi β-metilbutirato (HMB) es una estrategia para potenciar el entrenamiento físico a través de la hipertrofia de los músculos esqueléticos, pero otros tejidos como la próstata también pueden verse afectados. Los cambios en el tamaño y la función de la próstata están asociados con el comportamiento de las personas, pero la evidencia de una asociación con la suplementación es escasa. Por lo tanto, el objetivo de nuestro estudio fue evaluar el efecto de la suplementación con β-hidroxi βmetilbutirato (HMB) y el entrenamiento concurrente en la próstata. Las ratas Wistar se dividieron aleatoriamente en cuatro grupos con 10 animales cada uno: grupo de control (C), grupo suplementado (S), grupo de entrenamiento (T) y grupo de entrenamiento suplementado (TS). Los grupos suplementados (S y TS) recibieron 76 mg•kg / día de HMB y los grupos de entrenamiento concurrentes (T y TS) realizaron ejercicio tres veces por semana durante ocho semanas. HMB aumentó la composición corporal, el peso total de la próstata y alteró la histología de los compartimentos prostáticos. La próstata lateral de los animales en el grupo suplementado tuvo un aumento en los mastocitos por mm2 (28,0 ± 3,9) en comparación con el grupo de control y ejercicio (6,1 ± 3,0; 2,3 ± 0,9) También hubo un aumento de la inflamación en el estroma y la luz de la próstata, y aumento de la expresión del receptor de andrógenos (AR) en el grupo suplementado y entrenado (79,8 ± 2,1; 76,8 ± 11,4) en relación con el grupo entrenado (61,5 ± 7,0). Concluimos que el HMB altera los receptores de hormonas que inducen cambios morfológicos e inflamación, y los animales en el grupo de entrenamiento concurrente tenían perfiles inflamatorios y hormonales normales y una histología prostática favorable.

The effect of ß-hydroxy-ß-methylbutyrate (HMB) on the morphology of skeletal muscle after concurrent training

The aim of the present study was to investigate the effects of β-hydroxy-β-methylbutyrate (HMB) supplementation in association with concurrent training on morphological soleus muscle of rats. Wistar male rats were divided randomly into four groups: Control (C), Supplemented (S), Training (T) and Training + Supplemented (TS). Groups S and TS received 76mg/kg/day of HMB and the training groups (T and TS) were inserted into concurrent training program 3 times/week for 8 weeks. HMB had positive effects either on body composition of the animals or in type II muscle fibers. The concurrent exercise training was able in reducing the total fat mass as well as in increasing the diameter of muscle fibers. Our findings shows that HMB had an anti-catabolic effect with reference to the parameters of volume, weight and morphology of the soleus muscle, and there was a positive interaction between HMB supplementation and concurrent exercise training