scholarly journals Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1348
Author(s):  
Antonio J. León-González ◽  
Prudencio Sáez-Martínez ◽  
Juan M. Jiménez-Vacas ◽  
Vicente Herrero-Aguayo ◽  
Antonio J. Montero-Hidalgo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Colony Formation ◽  
Alkyl Ether ◽  
Beneficial Effects ◽  
Incidence And Mortality ◽  
Phosphorylation Pattern ◽  
Therapeutic Tools ◽  
Migration Capacity ◽  
Vitro Effect

A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Because of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.

scholarly journals Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
M. Olivan ◽  
M. Rigau ◽  
E. Colás ◽  
M. Garcia ◽  
M. Montes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Lipid Lowering ◽  
Concomitant Treatment ◽  
Simultaneous Treatment ◽  
Invasion And Migration ◽  
Beneficial Effects ◽  
Increased Risk ◽  
And Migration

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812),P<0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155),P=0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939),P<0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effectsin vitroare enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence.

LncRNA MEG3 inhibits the progression of prostate cancer by facilitating H3K27 trimethylation of EN2 through binding to EZH2

2019 ◽  
Vol 167 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Yaojun Zhou ◽  
Hongqiong Yang ◽  
Wei Xia ◽  
Li Cui ◽  
Renfang Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Colony Formation ◽  
H3k27 Trimethylation ◽  
Invasion And Migration ◽  
Over Expression ◽  
Pc3 Cells ◽  
Underlying Mechanisms ◽  
And Migration

Abstract This study aims to study the effects of intra-nuclear lncRNA MEG3 on the progression of prostate cancer and the underlying mechanisms. Expressions of relative molecules were detected by Quantitative real time PCR (qRT-PCR) and western blot. Chromatin immunoprecipitation and RNA immunoprecipitation (RIP) assays were used to evaluate the interaction between intra-nuclear MEG3, histone methyltransferase EZH2 and Engrailed-2 (EN2). The impacts of MEG3 on the viability, proliferation and invasion of prostate cancer cells (PC3) were evaluated by methyl thiazolyl tetrazolium, colony formation and transwell assays, respectively. PC3 cells were transfected with MEG3 and transplanted into nude mice to analyse the effect of MEG3 on tumourigenesis of PC3 cells in vivo. EN2 expression was inversely proportional to MEG3 in the prostate cancer tissues and PC3 cells. RIP results showed that intra-nuclear MEG3 could bind to EZH2. Knockdown of MEG3 and/or EZH2 up-regulated EN2 expression and reduced the recruitment of EZH2 and H3K27me3 to EN2, while over-expressed MEG3 caused opposite effects. MEG3 over-expression suppressed cell viability, colony formation, cell invasion and migration of PC3 cells in vitro and inhibited tumourigenesis of PC3 cells in vivo, while EN2 over-expression diminished the effects. These findings indicated that MEG3 facilitated H3K27 trimethylation of EN2 via binding to EZH2, thus suppressed the development of prostate cancer.

scholarly journals Quercetin and Its Nano-Scale Delivery Systems in Prostate Cancer Therapy: Paving the Way for Cancer Elimination and Reversing Chemoresistance

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1602
Author(s):  
Yaseen Hussain ◽  
Sepideh Mirzaei ◽  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Kiavash Hushmandi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fruits And Vegetables ◽  
Prostate Gland ◽  
Epidemiological Studies ◽  
Beneficial Effects ◽  
Synthetic Drugs ◽  
Cancer Agent ◽  
Underlying Mechanisms

Prostate cancer is the second most leading and prevalent malignancy around the world, following lung cancer. Prostate cancer is characterized by the uncontrolled growth of cells in the prostate gland. Prostate cancer morbidity and mortality have grown drastically, and intensive prostate cancer care is unlikely to produce adequate outcomes. The synthetic drugs for the treatment of prostate cancer in clinical practice face several challenges. Quercetin is a natural flavonoid found in fruits and vegetables. Apart from its beneficial effects, its plays a key role as an anti-cancer agent. Quercetin has shown anticancer potential, both alone and in combination. Therefore, the current study was designed to collect information from the literature regarding its therapeutic significance in the treatment of prostate cancer. Studies performed both in vitro and in vivo have confirmed that quercetin effectively prevents prostate cancer through different underlying mechanisms. Promising findings have also been achieved in clinical trials regarding the pharmacokinetics and human applications of quercetin. In the meantime, epidemiological studies have shown a negative correlation between the consumption of quercetin and the incidence of prostate cancer, and have indicated a chemopreventive effect of quercetin on prostate cancer in animal models. The major issues associated with quercetin are its low bioavailability and rapid metabolism, and these require priority attention. Chemoresistance is another main negative feature concerning prostate cancer treatment. This review highlights the chemotherapeutic effect, chemo preventive effect, and chemoresistance elimination potential of quercetin in prostate cancer. The underlying mechanisms for elimination of prostate cancer and eradication of resistance, either alone or in combination with other agents, are also discussed. In addition, the nanoscale delivery of quercetin is underpinned along with possible directions for future study.

scholarly journals Pharmacological properties of fireweed (Epilobium angustifolium L.) and bioavailability of ellagitannins. A review

2020 ◽  
Vol 66 (1) ◽  
pp. 52-64
Author(s):  
Mariola Dreger ◽  
Artur Adamczak ◽  
Katarzyna Seidler-Łożykowska ◽  
Karolina Wielgus
Keyword(s):  
Prostate Cancer ◽  
Cancer Chemoprevention ◽  
Antimicrobial Activities ◽  
Biological Properties ◽  
Pharmacological Properties ◽  
Beneficial Effects ◽  
Epilobium Angustifolium ◽  
The Individual

SummaryFireweed (Epilobium angustifolium L.) is a well-known medicinal plant traditionally used in the treatment of urogenital diseases, stomach and liver disorders, skin problems, etc. E. angustifolium extracts show anti-androgenic, antiproliferative, cytotoxic, antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial activities. The unique combination of biological properties demonstrated by the results of some studies indicates that fireweed has a positive effect in benign prostatic hyperplasia (BPH) and potentially in the prostate cancer chemoprevention. However, the efficacy of E. angustifolium phytotherapy is still poorly tested in clinical trials, while numerous beneficial effects of extracts have been documented in the in vitro and in vivo tests. Fireweed is rich in polyphenolic compounds, particularly ellagitannins. Currently, polyphenols are considered to be modulators of beneficial gut microbiota. The literature data support the use of ellagitannins in the prostate cancer chemoprevention, but caution is advised due to the highly variable production of urolithins by the individual microbiota. A better understanding of the microbiota’s role and the mechanisms of its action are crucial for an optimal therapeutic effect. This paper aims to summarize and discuss experimental data concerning pharmacological properties of E. angustifolium and bioavailability of ellagitannins – important bioactive compounds of this plant.

In Vitro and In Vivo Antimetastatic Effects of ZSTK474 on Prostate Cancer DU145 Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 321-329 ◽  
Author(s):  
Jie Liu ◽  
Xiao Tan ◽  
Wennan Zhao ◽  
Jing Liu ◽  
Xiaoxue Xing ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Structure ◽  
Treated Group ◽  
Adhesion Assay ◽  
Mineral Density ◽  
Migration Assay ◽  
Du145 Cells ◽  
Vitro Effect

Background: The lethality of prostate cancer is mainly due to metastasis. Inhibition of metastasis is expected to be a promising approach for prostate cancer therapy. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is reported to be closely involved in cell growth, migration, etc. Objective: The study investigated the antimetastatic activities of pan-PI3K inhibitor ZSTK474 on DU145 cells. Methods: 1. The In vitro effect of ZSTK474 on the migration, invasion and adhesion of DU145 cells was determined with Transwell migration assay and wound healing assay, Tranwell invasion assay and adhesion assay, respectively. 2. In vitro effect of ZSTK474 on the signal proteins in DU145 cells was determined with Western blot analysis and ELISA. 3. Moreover, the In vivo antimetastatic effect of ZSTK474 was evaluated with MicroCT and histology analysis. Results: ZSTK474 potently attenuated the capability of migration, invasion and adhesion of DU145 cells, negatively regulated Girdin, Integrinβ1 and matrix metalloproteinases (MMPs). In addition, the expression of hypoxia-inducible factor-1&#945; (HIF-1&#945;) and vascular endothelial growth factor (VEGF), which are known to be related to angiogenesis and metastasis, was also inhibited. Oral administration of ZSTK474 (200 mg/kg) ameliorated in vivo bone metastasis of DU145 cells, with improved bone structure and bone mineral density (BMD). Tissue staining indicated a reduction in metastatic DU145 cells and osteoclasts in the bones of ZSTK474-treated mice, compared with the non-treated group. Conclusion: Our result demonstrated the antimetastatic activity of ZSTK474 on prostate cancer DU145 cells, suggesting the potential application in prostate cancer patients.

Utilizing metformin as a radiosensitizing agent in the treatment of prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 89-89
Author(s):  
L. Klotz ◽  
N. Venier ◽  
A. Vandersluis ◽  
R. Besla ◽  
N. Fleshner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Combination Treatment ◽  
Colony Formation ◽  
Xenograft Model ◽  
External Beam Radiation ◽  
Diabetic Patients ◽  
Beam Radiation

89 Background: External beam radiation therapy (EBRT) is a well recognized curative prostate cancer (PCa) treatment modality utilizing ionizing radiation (IR). In addition to mediating DNA damage, IR upregulates several intracellular pro-survival pathways including the insulin- like growth factor (IGR) signaling network. This may contribute to the intrinsic radioresistance exhibited by certain tumors. Diabetic patients with PCa experience poorer outcomes following EBRT than their non-diabetic counterparts. Some attribute this to diabetes-induced chronic hyperinsulinemia with consequent upregulation of pro-survival insulin/IGF signalling. Previous work by our group showed diet-induced hyperinsulinemia to enhance PCa tumor growth in vivo. Metformin, a diabetic treatment, alleviates hyperinsulinemia, and also exhibits anti-neoplastic properties. We postulate that pre-treatment with metformin to correct hyperinsulinemia may protect cells from radiation-mediated pro-survival insulin/IGF signaling. Thus we assessed the radiosensitizing potential of metformin using in vitro and in vivo PCa models. Methods: The effect of IR and/or metformin on colony formation rates was assessed in LNCaP, PC3, DU145 and PC3AR2 PCa cell lines using clonogenic assay. The combination treatment regimen was assessed in vivo using a murine xenograft model. Western blot and cell cycle analyses are ongoing to try and elucidate any mechanisms of interaction between metformin and IR. Results: Monotherapy with IR (1-8Gy) or metformin (0.01-10.0mM) caused significant dose-dependent reduction in colony formation rates (p<0.001). Combination treatment further significantly reduced colony formation rates (p<0.03). Preliminary results from our in vivo study show diminished tumor growth in response to combination treatment (p<0.0001), and are currently subject to ongoing statistical analyses. Conclusions: Our in vitro findings confirm combining metformin with IR significantly reduces PCa cell colony formation rates further than either monotherapy. Recapitulation of these results in vivo would provide justification for translating this work into a phase II clinical trial of metformin as a radiosensitizing agent. No significant financial relationships to disclose.

scholarly journals Impregnation of Curcumin into a Biodegradable (Poly-lactic-co-glycolic acid, PLGA) Support, to Transfer Its Well Known In Vitro Effect to an In Vivo Prostate Cancer Model

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2312 ◽  
Author(s):  
Eulalio Gracia ◽  
Andrea Mancini ◽  
Alessandro Colapietro ◽  
Cristina Mateo ◽  
Ignacio Gracia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glycolic Acid ◽  
Curcuma Longa ◽  
Subcutaneous Administration ◽  
Uv Spectrophotometry ◽  
Medicinal Plant Extracts ◽  
Biodegradable Poly ◽  
Vitro Effect

Prostate cancer (PCa) is one of the most common cancers in older men and is associated with high mortality. Despite advances in screening for early detection of PCa, a large proportion of patients continue to be diagnosed with metastatic disease, with ~20% of men showing a high tumor grade and stage. Medicinal plant extracts have a great potential to prevent/treat PCa, as well as to reduce its incidence/prevalence and improve survival rates. One of the most promising extracts is curcumin, which is a major, nontoxic, bioactive compound of Curcuma longa. Curcumin has strong antitumor activity in vitro. However, its potential beneficial in vivo affects are limited by its low intestinal absorption and rapid metabolism. In this study, curcumin was impregnated into a biodegradable poly(lactic-co-glycolic) acid (PLGA) support and characterized by FTIR and DSC, and its release by UV spectrophotometry. PLGA-curcumin was tested in different subcutaneous PCa xenograft models (PC3, 22rv1, and DU145 PCa cell-lines), and its effects evaluated by tumor progression an immuno-histochemical analysis (Trichromic, Ki67 and TUNEL stainings), were compared with those of a commercial curcumin preparation. Our results indicate that curcumin-impregnated PLGA is significantly more active (~2-fold increase) with respect to oral curcumin, which supports its use for subcutaneous administration.

Sign in / Sign up

Export Citation Format

Share Document