Prostate Cell Growth Research Articles

Advances in Prostate Cancer Immunotherapy: Current Options and Emerging Novel Approaches

Prostate cancer (PCa) is a significant malignancy in men, contributing considerably to the rise in male mortality rates worldwide. Men diagnosed with PCa may have either localized or advanced stages of the disease. Globally, it ranks as the second most common and fifth most aggressive cancer type in males. The likelihood of developing prostate cancer in a man’s lifetime is approximately one in seven. Epidemiological research has linked various environmental and genetic factors to the abnormal growth of prostate cells, which leads to the formation of cancerous cells. Men experiencing a recurrence of prostate cancer or presenting with metastasis typically undergo androgen deprivation therapy (ADT), along with salvage radiotherapy and chemotherapy. While current treatment methods are more effective when used in combination, prostate cancer remains incurable. Research efforts are focused on exploring alternative treatments, including traditional medicine, nanotechnology applications, and gene therapy, to address drug resistance and mitigate the side effects associated with existing treatments. This article provides an overview the current treatment methods, and ongoing research into new treatment alternatives.

Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway

Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.

Role of Vitamins in Therapeutic and Targeting Approaches for Prostate Cancer: An Overview.

Vitamins play a crucial role in cellular functions like cell cycling and proliferation, differentiation, and apoptosis. These also help in the induction of cell cycle arrest and/or apoptosis. They can inhibit normal prostatic epithelial cell growth and might be helpful for the prevention of prostate cancer (PCa). Many essential vitamins including the fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K) and the water-soluble vitamins (vitamin B complexes and vitamin C) have a huge impact on the inhibition of growth and progression of PCa. Vitamins show anticancer properties and are involved in regulatory processes like the DNA repairing process, which inhibit the growth of PCa. Consumption of multivitamins prevents methylation of cancer cells and possesses an enormous potential that can be applied for the prevention as well as in the management of PCa. They have a great role in the inhibition of different signalling pathways involved in PCa. Moreover, they have also displayed a significant role in targeting of PCa with various nanocarrier systems. This review encompasses the recent studies about the individual actions of different vitamins and vitamin analogs, the combination of vitamins, and their efficient functions in various therapeutic and targeting approaches for PCa.

Exploring novel Apalutamide analogues as potential therapeutics for prostate cancer: design, molecular docking investigations and molecular dynamics simulation.

Introduction: Prostate cancer (PC) ranks as the second most frequent type of cancer in men and is the fourth largest cause of mortality worldwide. Androgenic hormones such as testosterone and dihydrotestosterone are crucial for the development and progression of the prostate gland. Androgenic hormones bind to androgen receptors (AR) and trigger the synthesis of many genes that stimulate the growth of prostate cells, initiating PC growth. Apalutamide (APL) is a non-steroidal antiandrogen drug used to treat PC; however, it also causes a variety of toxicities and resistance during the treatment. Methods: The purpose of this study was to computationally identify new and safer analogues of APL, focusing on improved pharmacokinetic properties and reduced toxicity. Drug likeness (DL) and drug score (DS) were also calculated. Docking studies on the designed analogues were conducted to predict their binding affinities and compare their orientations with the ligands in the original crystal structure. Molecular dynamics (MD) simulation of docked ligands was done using Schrödinger suite. Results: We generated a total of 1,415 analogues for different groups of APL using the bioisosteric approach. We selected 80 bioisosteres based on pharmacokinetic profiles, DL and DS score predictions, and found that the designed APL bioisosteres were optimal to good compared to APL. Analogues APL19, APL35, APL43, APL76, and APL80, formed hydrogen bonds with protein (PDB ID: 5T8E) which is similar hydrogen bonding to the standard (APL). The MD simulation result confirmed that APL43 and APL80 complexes were stable during the 100nS run. Discussion: The results suggest that the APL analogues, particularly APL43 and APL80, are predicted to be potential antiandrogen drugs for the treatment of prostate cancer.

Ixeris polycephala Extract Alleviates Progression of Benign Prostatic Hyperplasia via Modification of Proliferation, Apoptosis, and Inflammation.

Benign prostatic hyperplasia (BPH) is a urogenital disorder that is common in aging men. Ixeris polycephala (IP) is used in traditional medicine and contains pharmacologically active compounds. However, the effect for BPH progression has not been elucidated. We herein examined the protective potential of IP extract on a testosterone-induced model of BPH in rats. To generate the BPH model, daily subcutaneous administration of testosterone was applied for 4 weeks. During this period, the rats were also administered a daily oral gavage of IP (150 mg/kg), finasteride (positive control), or vehicle. Testosterone treatment was associated with a significantly higher prostate-to-body weight ratio, serum dihydrotestosterone (DHT) level, and prostatic gene expression of 5α-reductase compared to untreated controls. Notably, IP plus testosterone co-treatment was associated with decreased epithelial thickness, down-regulation of proliferating cell nuclear antigen (PCNA) and cyclin D1, and upregulation of pro-apoptotic signaling molecules. IP co-treatment also down-regulated pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and decreased inflammatory cell infiltration compared to the levels seen in the testosterone-induced BPH. IP appears to protect rats against the progression of testosterone-induced BPH by alleviating prostate cell growth and inflammatory responses, and thus may have potential for clinical use against BPH progression.

Abstract 462: Developing the miR-888 cluster as a therapeutic target for prostate cancer

Abstract Prostate Cancer (PCa) is a serious health crisis in the United States. 20% of men diagnosed with PCa will progress to fast-growing, advanced disease. There are no curative treatment options for PCa that has spread to distant sites and the 5-year survival rate for metastatic disease remains 30%. Recognizing the need for better PCa therapeutics, we are developing novel anti-microRNA delivery reagents targeted against the noncoding RNA miR-888 cluster to block prostate tumor progression. Our lab identified these oncomiRs in a biomarker discovery screen as elevated in human metastatic PCa cell lines and prostatic fluids from patients with high-grade PCa. We noted that over-expression of miR-888 cluster members (miR-888, miR-891a) promoted prostate cell growth and induced invasiveness in vitro. miR-888 and miR-891a also accelerated xenograft tumor growth in mice. Treatment of aggressive PCa cells in culture with synthetic antisense inhibitors against individual cluster members reversed these growth and invasion phenotypes, highlighting their clinical potential. We are testing pH Low Insertion Peptide (pHLIP)-Peptide Nucleic Acid (PNA)-based antimiR conjugates against miR-888 and miR-891a. The delivery vehicle pHLIP is a 36-amino acid peptide that at low pH (< pH 6.5) adopts an alpha-helical conformational change and facilitates the insertion of its C-terminus across lipid bilayers to transport conjugated anti-miRNA cargo into cells. When administered systemically, pHLIP effectively targets solid tumors with acidic microenvironments. We found that these reagents are readily internalized by human PCa cells cultured at pH 6.0 and in prostate xenograft tumors when delivered systemically in mice. Treatment significantly repressed miR-888 and miR-891a and acted to slow prostate cell growth in vitro. We are currently moving these studies into mouse prostate models. Furthermore, we are investigating the downstream signaling pathways for the miR-888 cluster. Our work indicates that the miR-888 cluster network coordinates the repression of the Tissue Inhibitors of Metalloproteinase (TIMP) and SMAD4 anti-metastatic pathways to drive extracellular matrix degradation and prostate cell invasion, and as a consequence, induces matrix metalloproteinase (MMP) activity. Expression profiling arrays and luciferase reporter assays indicated that multiple members of the miR-888 cluster co-suppress TIMPs in the prostate and similarly elevate multiple MMPs as well as cadherins, fibronectin and heparinase, and co-modulated several immune response genes. We are currently studying the consequence of various CRISPR-mediated miR-888 cluster deletions to understand how this non-coding RNA cluster functionally overlaps to promote aggressive PCa. This work will establish new clinical tools for aggressive PCa and optimize patient treatment management. Citation Format: Katherine Routon, Trevor Fachko, Vishal Kasina, Raman Bahal, Aurora Esquela Kerscher. Developing the miR-888 cluster as a therapeutic target for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 462.

Protective Effect of Panicum dichotomiflorum in a Rodent Model of Testosterone-Induced Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a common disease in aging men. Panicum dichotomiflorum (PD) is an annual grass species of Poaceae that is distributed worldwide. The present study examined whether PD has a protective effect against BPH. BPH was generated in rats by daily subcutaneous administration of testosterone for four weeks. During this period, the rats were also given daily oral gavages of an extract of PD (150 mg/kg). After the final treatment, all animals were euthanized and their prostates were collected and weighed. In BPH model rats, the prostate weight and levels of dihydrotestosterone (DHT) and 5α-reductase expression were inhibited following treatment with PD extract. Testosterone-induced increases in prostate gland epithelial thickness and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) were markedly suppressed in PD-treated rats, whereas cleaved caspase-3 levels were increased. PD administration also decreased the expression of transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF), the phosphorylation of Akt, and inflammatory cytokines levels. Taken together, these results show that PD extract protects against testosterone-induced BPH progression by alleviating prostate cell growth and reducing levels of growth factors and inflammatory cytokines, indicating that PD extract may have potential in protecting against BPH.

Thyroid Nodule Correlation with Serum Prolactin and TPO Antibody Levels: A Case-Control Study

Introduction: The prevalence of thyroid nodules poses a grave clinical concern as they may lead to malignancy. Prolactin has been found to have anti-cell death properties and stimulates the growth of breast and prostate cells, as has been discovered in exploratory examinations. In light of this, the current research was designed to investigate whether a possible relationship exists between thyroid nodules and serum prolactin levels. Material and Methods: Ninety participants were enrolled in this study, of which 60 presented with thyroid nodules (30 antithyroid peroxidase antibody (TPO-Ab) positive and 30 TPO-Ab negative) and 30 without thyroid nodules (control group). Patients' serum prolactin, TPO-Ab, thyroid-stimulating hormone (TSH), T4 values, and thyroid ultrasound reports were scrutinized. Statistically significant outcomes were determined by a P-value less than 0.05. Results: Serum TSH, prolactin, and TPO-Ab levels were significantly higher in the case group than in the control group (P=0.041, 0.050, and 0.000, respectively). The case group had more instances of hyperprolactinemia than the control group (35% vs. 13.3%) (OR=3.5, CI 95%=1.08-11.38, P=0.031). Furthermore, the TPO-Ab positive group demonstrated greater solidity than the TPO-Ab negative group (93.3% vs. 73.3%, P=0.038). Conclusion: The present study confirmed the presence of a positive correlation between thyroid nodules and increased serum TSH, prolactin, and TPO-Ab levels. Furthermore, TPO-Ab positive nodules exhibited greater solidity and elevated TSH levels.

An In-Depth Look Into the Epidemiological and Etiological Aspects of Prostate Cancer: A Literature Review.

Prostate cancer is the second most frequently diagnosed cancer among men worldwide, and it represents a substantial worldwide health issue, primarily impacting men as they grow older. Understanding its epidemiology and etiology is crucial for crafting efficient preventive measures and enhancing treatment results. The epidemiology of this disease provides valuable insights into its prevalence and distribution. Age is a critical factor, with the risk of prostate cancer increasing with advancing years. Incidence rates are notably higher in developed countries, suggesting a role for lifestyle and environmental factors. Furthermore, there are significant racial and geographical disparities in prostate cancer incidence, with African-American men experiencing both a higher incidence and more aggressive forms of the disease. On the other hand, hormones, especially testosterone and its conversion to dihydrotestosterone (DHT), contribute to prostate cell growth and, potentially, cancer. Genetics also plays a pivotal role, with certain gene mutations, like Breast Cancer gene 1 & 2 (BRCA1 and BRCA2), elevating risk. Dietary habits and lifestyle choices influence susceptibility, with diets low in fruits and vegetables and high in saturated fats linked to higher risk. Chronic inflammation, often tied to prostatitis, may further increase susceptibility to prostate cancer. This review article explores the complex realm of prostate cancer, providing insights into its occurrence, factors that elevate risks, and the fundamental factors that play a role in its emergence and how we can prevent it.

Benign prostatic hyperplasia and the urinary tract repercussions

Known as the most common urological disease, benign prostatic hyperplasia (BPH) is a condition that affects men from 40 years of age. Linked to metabolic, hormonal and inflammatory mechanisms, the disease causes growth of prostatic tissue, epithelial and stromal cells, compressing the urethra, resulting in resistance to the output of urine from the bladder and the main complaints of the disease, the symptoms of the lower urinary tract (LUTS). This study aims to inform about benign prostatic hyperplasia and its main symptoms of the lower urinary tract, since these LUTS negatively affect affected patients. This is a literature review with articles published on the subject in the last 7 years, through an electronic search in the main bibliographic indexes. The benign growth of the prostate gland and its obstructive and irritating urinary symptoms such as: urgency to urinate, hesitation, forced urination with slow flow, nocturia and irritation, negatively affect the quality of life of most patients. Diagnosed in a simple way, based on the patient's clinical history, physical examination and digital rectal examination, in addition to laboratory and imaging tests, such as transrectal ultrasound, BPH has an excellent prognosis. For the treatment, the degree of the patient's symptoms is evaluated through a questionnaire, the International Prostate Symptom Score (IPSS), the classification in mild, moderate and severe defines the conduct. Watchful waiting, a treatment for patients with mild symptoms, is the most common. The existing drug classes aim to reduce LUTS and slow down the progression of the disease. The growth of the prostate gland and the consequent compression of the urethra, causes several complaints and losses in the daily life of men who have BPH, therefore, knowing the signs and symptoms of the disease is essential for it to be effectively diagnosed and treated.

Biocompatibility and efficacy of prostatic urethral lift in benign prostate hyperplasia: an in vivo and in vitro study

The study aimed to assess the biocompatibility and efficacy of a prostatic urethral lift (PUL) for benign prostatic hyperplasia (BPH). Human BPH-1 cells were co-cultured with implant anchors and sutures, and cytotoxicity was measured. Scanning electron microscopy (SEM) was used to observe adhesion and growth of cells and to evaluate implant biocompatibility. Fifteen male beagle dogs were randomly assigned to the surgical (n = 9) or sham-operated (n = 6) groups. The surgical group underwent cystotomy, and PUL was used to insert two implants in each lobe of the prostate to compress the enlarged prostate and dilate the urethra; the sham group underwent cystotomy without implant insertion. Compared with the control group, no significant difference in cell viability among the groups with different co-culture times of implant anchors and sutures (P > 0.05) was observed. SEM revealed good adhesion and growth of prostate cells on the implants. Improvements in urine flow rates remained stable at 7, 28, and 180 days after surgery, and the urethral diameter in the prostate region was significantly increased compared with that before surgery. PUL is a biocompatible and effective treatment for BPH, improving the urine flow rate without causing inflammation, tissue damage, or cytotoxic effects. Here, the basis for further PUL application was provided.

N-(2-ozoazepan-3-yl)-pyrrolidine-2-carboxamide, a novel Octopus vulgaris ink-derived metabolite, exhibits a pro-apoptotic effect on A549 cancer cell line and inhibits pro-inflammatory markers.

This research aimed to chemically synthesize and evaluate the antiproliferative and anti-inflammatory potential of ozopromide (OPC), a novel compound recently isolated from O. vulgaris ink. After chemical synthesis, OPC structural characterization was confirmed by COSY2D, FTIR, and C-/H-NMR. OPC inhibited the growth of human breast (MDA-MB-231), prostate (22Rv1), cervix (HeLa), and lung (A549) cancerous cells, being the highest effect on the latter (IC50: 53.70μM). As confirmed by flow cytometry, OPC induced typical apoptosis-derived morphological features on A549cells, mostly at early and late apoptosis stages. OPC generated a dose-dependent effect inhibiting IL-6 and IL-8 on LPS-stimulated peripheral mononuclear cells (PBMCs). A major affinity of OPC to Akt-1 and Bcl-2 proteins in silico agreed with the observed pro-apoptotic mechanisms. Results suggested that OPC has the potential to alleviate inflammation and be further studied for anticancer activity. Marine-derived food products such as ink contains bioactive metabolites exhibiting potential health benefits.

The prognostic value of androgen to PSA ratio in predictive modeling of prostate cancer

Prostate specific antigen (PSA) is the ubiquitous biomarker used in mathematical and artificial intelligence models of prostate cancer. Yet, it is imperfect. The growth of prostate and cancer cells produces PSA, but their growth is dependent on androgen in most cases. Thus, looking at PSA by itself ignores the impact of androgen. Here, we propose the use of androgen as a reference framework for better integration of PSA in prostate cancer models. The binding of androgen to androgen receptors activates signals that promote prostate cancer growth and the production of PSA, so higher levels of androgen should correlate to higher growth of the tumor and higher production of PSA. Thus, PSA and androgen fall and rise almost synchronously during the start and stop of androgen deprivation therapy (ADT), respectively. Yet, when cancer cells become resistant to ADT, we observe a divergence to this trend, leading to a high level of PSA even during ADT. Therefore, we hypothesize that the cancer evolutionary dynamics can be represented by the ratio of androgen to PSA and its integration into prostate cancer models may help improve their predictive power.

Infinity war: Trichomonas vaginalis and interactions with host immune response

Trichomonas vaginalis is the pathological agent of human trichomoniasis. The incidence is 156 million cases worldwide. Due to the increasing resistance of isolates to approved drugs and clinical complications that include increased risk in the acquisition and transmission of HIV, cervical and prostate cancer, and adverse outcomes during pregnancy, increasing our understanding of the pathogen's interaction with the host immune response is essential. Production of cytokines and cells of innate immunity: Neutrophils and macrophages are the main cells involved in the fight against the parasite, while IL-8, IL-6 and TNF-α are the most produced cytokines in response to this infection. Clinical complications: T. vaginalis increases the acquisition of HIV, stimulates the invasiveness and growth of prostate cells, and generates an inflammatory environment that may lead to preterm birth. Endosymbiosis: Mycoplasma hominis increased cytotoxicity, growth, and survival rate of the parasite. Purinergic signaling: NTPD-ases and ecto-5'-nucleotidase helps in parasite survival by modulating the nucleotides levels in the microenvironment. Antibodies: IgG was detected in serum samples of rodents infected with isolates from symptomatic patients as well as patients with symptoms. However, antibody production does not protect against a reinfection. Vaccine candidate targets: The transient receptor potential- like channel of T. vaginalis (TvTRPV), cysteine peptidase, and α-actinin are currently cited as candidate targets for vaccine development. In this context, the understanding of mechanisms involved in the host-T. vaginalis interaction that elicit the immune response may contribute to the development of new targets to combat trichomoniasis.

Activin B and Activin C Have Opposing Effects on Prostate Cancer Progression and Cell Growth

Current prognostic and diagnostic tests for prostate cancer are not able to accurately distinguish between aggressive and latent cancer. Members of the transforming growth factor-β (TGFB) family are known to be important in regulating prostate cell growth and some have been shown to be dysregulated in prostate cancer. Therefore, the aims of this study were to examine expression of TGFB family members in primary prostate tumour tissue and the phenotypic effect of activins on prostate cell growth. Tissue cores of prostate adenocarcinoma and normal prostate were immuno-stained and protein expression was compared between samples with different Gleason grades. The effect of exogenous treatment with, or overexpression of, activins on prostate cell line growth and migration was examined. Activin B expression was increased in cores containing higher Gleason patterns and overexpression of activin B inhibited growth of PNT1A cells but increased growth and migration of the metastatic PC3 cells compared to empty vector controls. In contrast, activin C expression decreased in higher Gleason grades and overexpression increased growth of PNT1A cells and decreased growth of PC3 cells. In conclusion, increased activin B and decreased activin C expression is associated with increasing prostate tumor grade and therefore have potential as prognostic markers of aggressive prostate cancer.

Retraction Note: CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus.

Retraction Note: CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus.

Prostate health in India (BPH & Prostate Cancer)

The prostate gland, found only in men, is an extremely important organ of the reproductive system, but it is not taken care of adequately, leading to prostate inflammation and benign hypertrophy or even cancer. Benign prostate enlargement compresses urine flow through the urethra, leading to uncomfortable urinary symptoms. Hyperplasia increases the risk of bladder stones, urinary tract infections, and kidney problems. In India prevalence of Benign Prostrate Hyperplasia (BPH) is around 50% of men by the age of 60 years. Studies suggest that benign prostatic hyperplasia is a result of the disproportion between oestrogen & testosterone. A higher proportion of oestrogen within the prostate boosts the growth of prostate cells. The management of BPH is streamlined in recent times and the majority are on medical treatment. Prostate cancers are one of the cancers showing a significant increase in incidence along with mouth and kidney and lung cancers among the male population. With an estimated population of 1400 million and about 98 million males over 50 years of age in mid-2022 and the average life expectancy increasing 68.4 years, has a bearing on the changing incidence and pattern of prostate cancer in the current decade in India. Based on the five population-based cancer registries in 2009-10, the age-adjusted annual incidence rates per lakh population of prostate cancers were highest in Delhi (10.2) followed by Bengaluru (8.7), Mumbai (7.3), Chennai (7) and Bhopal (6.1). Cancer can co-exist with BPH. Prostate cancer management is still in the development stage with a 5-year life expectancy of around 64%. The prostate is the second leading site of cancer among males in large Indian cities like Delhi, Kolkata, Pune, and Thiruvananthapuram, and the third leading site of cancer in cities like Bangalore and Mumbai. Despite the limitations of diagnosis, the annual cancer incidence rate ranges from 5.0-9.1 per 100,000/year, as compared to the rates in the United States and other developed countries of 110 &180 for whites and blacks respectively. This article is a review of Prostate health in India based on a personal observation of around 183 cases by the author in the last 10 years. Materials & methods: This is an observational study report of three cohorts of men across the country. The sample was of people encountering the author. The sample included i) 69 septuagenarians plus ii) 30 senior citizens aged 60 - 70 years and iii) 84 men in 40 – 60 - year age groups over the last decade. The data source was sharing annual check-up reports or consultation report in person for seeking 2nd opinion. A minimum of 2 consultations, first when diagnosed and the recent between July 2021 to June 2022.

Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3

sBenign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.

Differential In Vitro Growth and Cell Killing of Cancer versus Benign Prostate Cells by Oncolytic Parainfluenza Virus.

The development of effective oncolytic viruses will require understanding the differences in virus replication and killing between normal and cancer cells. Here, we have evaluated infections of metastatic cancer (22Rv1) and benign non-tumorigenic (BPH-1) prostate cell lines with a mutant parainfluenza virus 5 (P/V/F) encoding a defective V protein and a hyperfusogenic F protein. Under low multiplicity of infection (MOI), the P/V/F mutant efficiently spread in 22Rv1 cells but was restricted in BPH-1 cells due to type-I interferon (IFN-I) responses. In mixed co-cultures, the P/V/F mutant showed specificity towards and spread within the 22Rv1 cells versus BPH-1 cells. Under high MOI conditions, both BPH-1 and 22Rv1 cells showed efficient infection by the P/V/F mutant. However, compared to BPH-1 cells, the 22Rv1 cancer cells showed increased cytopathic effect, higher induction of caspase-8 and -9, and extensive syncytia formation. In 22Rv1 spheroid cultures, P/V/F infection was less efficient compared to monolayers, but the virus was able to spread through spheroids and induce death. These data indicate that IFN-I sensitivity is a major determinant of specificity of P/V/F spread through populations of cancer versus benign cells, and additionally, differences in activation of apoptotic pathways and syncytia formation can contribute to differential outcomes in cancer versus benign cells.

Treatment of Benign Prostatic Hyperplasia by Natural Drugs.

Benign prostatic hyperplasia (BPH) is one of the most common urinary diseases affecting men, generally after the age of 50. The prevalence of this multifactorial disease increases with age. With aging, the plasma level of testosterone decreases, as well as the testosterone/estrogen ratio, resulting in increased estrogen activity, which may facilitate the hyperplasia of the prostate cells. Another theory focuses on dihydrotestosterone (DHT) and the activity of the enzyme 5α-reductase, which converts testosterone to DHT. In older men, the activity of this enzyme increases, leading to a decreased testosterone/DHT ratio. DHT may promote prostate cell growth, resulting in hyperplasia. Some medicinal plants and their compounds act by modulating this enzyme, and have the above-mentioned targets. This review focuses on herbal drugs that are most widely used in the treatment of BPH, including pumpkin seed, willow herb, tomato, maritime pine bark, Pygeum africanum bark, rye pollen, saw palmetto fruit, and nettle root, highlighting the latest results of preclinical and clinical studies, as well as safety issues. In addition, the pharmaceutical care and other therapeutic options of BPH, including pharmacotherapy and surgical options, are discussed, summarizing and comparing the advantages and disadvantages of each therapy.