scholarly journals Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment

2021 ◽  
Vol 11 (1) ◽  
pp. 298-311
Author(s):  
Read F. Alserihi ◽  
Mohammed Razeeth Shait Mohammed ◽  
Mohammed Kaleem ◽  
Mohammad Imran Khan ◽  
Mario Sechi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Folate Receptor ◽  
3D Culture ◽  
Analytical Techniques ◽  
Anticancer Efficacy ◽  
Species Formation ◽  
22Rv1 Cell ◽  
Human Folate Receptor

Abstract In continuation of our previous studies, we developed polymeric epigallocatechin 3-gallate (EGCG)-loaded nanoparticles (NPs) coupled with folic acid (FA), able to dually bind the human folate receptor alpha (FOLR1), and prostate-specific membrane antigen (PSMA+) in prostate cancer (PCa) model. After a preliminary computational molecular recognition of NP′ ligand binding on the FOLR1 active site, we synthesized the biocompatible block-copolymer PLGA–PEG–FA to prepare EGCG-targeted NPs (EGCG-T-NPs). The obtained NPs were characterized by various analytical techniques, and anticancer efficacy was determined by different sets of experiments in a 3D culture of PCa using PC3 and 22Rv1 cell lines. Results showed a significant reduction in spheroid size by EGCG-T-NPs, especially in PSMA+ (22Rv1) cells. The targeted NPs significantly enhanced the antiproliferative activity of EGCG against PCa cell lines, especially toward the PSMA+ cells, known to have higher FOLR1 expression. We did not observe any changes in the reactive oxygen species formation in both studied cell lines. However, significant changes in mitochondrial depolarization (15%) and polarization (18%) were recorded in response to EGCG-T-NP compared to control in 22Rv1. Similarly, EGCG-T-NP treatment also showed an increase in the number of dead apoptotic cells in 22Rv1 spheroids. Collectively, the obtained results support our hypothesis about the role of these targeted nanoprototypes in the increasing cellular uptake of EGCG payload into PCa cells, thus enhancing its antitumor efficacy.

scholarly journals IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9

2013 ◽  
Vol 20 (5) ◽  
pp. 677-689 ◽  
Author(s):  
Holger H H Erb ◽  
Regina V Langlechner ◽  
Patrizia L Moser ◽  
Florian Handle ◽  
Tineke Casneuf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Tissue Expression ◽  
Type I ◽  
Regulatory Factor ◽  
Quantitative Real Time Pcr ◽  
Antiproliferative Effects ◽  
Protein Levels

Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.

scholarly journals Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

2015 ◽  
Vol 23 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Jan Kroon ◽  
Martin Puhr ◽  
Jeroen T Buijs ◽  
Geertje van der Horst ◽  
Daniëlle M Hemmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glucocorticoid Receptor ◽  
Cell Lines ◽  
Chemotherapy Resistance ◽  
Clinical Problem ◽  
Dependent Manner ◽  
Ru 486 ◽  
Docetaxel Resistance ◽  
Docetaxel Treatment

Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa.

Role of JMJD3 Demethylase and Its Inhibitor GSK-J4 in Regulation of MGMT, TRA2A, RPS6KA2, and U2AF1 Genes in Prostate Cancer Cell Lines

2020 ◽  
Vol 24 (8) ◽  
pp. 505-507
Author(s):  
Anna Sanchez ◽  
Driss El Ouardi ◽  
Fatma Zohra Houfaf Khoufaf ◽  
Mouhamed Idrissou ◽  
Tiphanie Boisnier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines

scholarly journals Role of a novel race-related tumor suppressor microRNA located in frequently deleted chromosomal locus 8p21 in prostate cancer progression

2019 ◽  
Vol 40 (5) ◽  
pp. 633-642 ◽  
Author(s):  
Divya Bhagirath ◽  
Thao Ly Yang ◽  
Z Laura Tabatabai ◽  
Varahram Shahryari ◽  
Shahana Majid ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Tumor Grade ◽  
Clinical Samples ◽  
Mesenchymal Transition ◽  
Microrna Genes

Abstract The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21–22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this region is associated with a set of microRNA genes—miR-3622, miR-3622b, miR-383—that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chromosome 8p—miR-4288—by employing clinical samples and cell lines. Our data suggests that (i) miR-4288 is widely downregulated in primary prostate tumors and cell lines; (ii) miR-4288 expression is lost in metastatic castration-resistant PCa; (ii) miR-4288 downregulation is race-related PCa alteration that is prevalent in Caucasian patients and not in African Americans; (iii) in Caucasians, miR-4288 was found to be associated with increasing tumor grade and high serum prostate-specific antigen, suggesting that miR-4288 downregulation/loss may be associated with tumor progression specifically in Caucasians; (iv) miR-4288 possess significant potential as a molecular biomarker to predict aggressiveness/metastasis; and (v) miR-4288 is anti-proliferative, is anti-invasive and inhibits epithelial-to-mesenchymal transition; and (vi) miR-4288 directly represses expression of metastasis/invasion-associated genes MMP16 and ROCK1. Thus, the present study demonstrates a tumor suppressor role for a novel miRNA located with a frequently lost region in PCa, strengthening our hypothesis that this locus is causally related to PCa disease progression via loss of microRNA genes. Our study suggests that miR-4288 may be a novel biomarker and therapeutic target, particularly in Caucasians.

500 USING THREE-DIMENSIONAL (3D) CULTURE SYSTEMS TO DELINEATE THE ROLE OF RANKL IN METASTATIC PROSTATE CANCER

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Shabnam Ziaee ◽  
Shirly Sieh ◽  
Gina C-Y. Chu ◽  
Ruoxiang Wang ◽  
Dietmar Hutmacher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Three Dimensional ◽  
3D Culture ◽  
Culture Systems

scholarly journals KIF15 is An Oncogene of Prostate Cancer and is A Key Prognostic Factor in Patients with Prostate Cancer

2021 ◽  
Author(s):  
Lin Li ◽  
Jing Hao ◽  
Jin-Xiu Liu ◽  
Peng-Fei Wang ◽  
Chao-Fei Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Cell Lines ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Metastatic Potential ◽  
Vital Role ◽  
Normal Tissues ◽  
Kinesin Superfamily

Abstract Background KIF15, a member of kinesin superfamily proteins, has been found that play a of vital role in the carcinogenesis of various malignant tumor. But whether KIF15 can facilitate the evolution of prostate cancer (PCa) is still unknown. This study aims to explore its biological function in PCa cells and its relevance to prognosis and clinical features in PCa patients. Material and Methods KIF15 expression at mRNA and protein level in tumor and normal tissues was detected by quantitative real-time PCR (RT-PCR) and immunohistochemistry. Then the correlations between KIF15 expression and PCa patients’ clinical characteristics was analyzed. After inhibiting the expression of KIF15 by shRNA, the role of KIF15 on proliferative capacity of PCa was evaluated by using MTT assay. The function of KIF15 on metastatic potential of PCa was determined by using transwell assay. The prognostic value of KIF15 was determined by using bioinformatics analysis. Results Compared with normal tissues, KIF15 was overexpressed in PCa tissues. After knocking down KIF15 in C4-2 and Lncap cell lines, the proliferation (P < 0.001) and invasion (P < 0.001) capabilities of tumor cells are significantly reduced compared to the shCON group. The proliferation marker Ki67 and the metastasis-related marker MMP9 were also significantly reduced in two cell lines after silencing KIF15. Except that, increased KIF15 in tumor tissue is associated with clinical stage (P = 0.004), seminal vesicle invasion (P = 0.02), lymph node metastasis (P = 0.03), and poor disease-free survival (P < 0.05) in PCa patients. Conclusions The results proved that KIF15 might served as a prognostic factor and therapeutic target in prostate cancer, and play as a vital regulatory factor in tumorigenesis and cancer development of prostate cancer.

scholarly journals TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 3936 ◽  
Author(s):  
Yohei Sekino ◽  
Xiangrui Han ◽  
Takafumi Kawaguchi ◽  
Takashi Babasaki ◽  
Keisuke Goto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Resistant Cell ◽  
Pi3k Inhibitor ◽  
Pten Expression ◽  
Cross Resistance ◽  
Pi3k Inhibitor Ly294002 ◽  
Resistant Cells

Recent studies have reported that TUBB3 overexpression is involved in docetaxel (DTX) resistance in prostate cancer (PCa). The aim of this study was to clarify the role of TUBB3 in DTX and cabazitaxel (CBZ) resistance, and cross-resistance between DTX and CBZ in PCa. We analyzed the effect of TUBB3 knockdown on DTX and CBZ resistance and examined the interaction between TUBB3 and PTEN. We also investigated the role of phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) in DTX and CBZ resistance. TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression. LY294002 suppressed TUBB3 expression in DTX-resistant and CBZ-resistant cell lines. LY294002 re-sensitized DTX-resistant cell lines to DTX and CBZ-resistant cell lines to CBZ. These results suggest that TUBB3 is involved in DTX resistance and CBZ resistance. A combination of LY294002/DTX and that of LY294002/CBZ could be potential strategies for PCa treatment.

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