scholarly journals Aquaglyceroporin-3’s Expression and Cellular Localization Is Differentially Modulated by Hypoxia in Prostate Cancer Cell Lines

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 838
Author(s):  
Andreia de Almeida ◽  
Dimitris Parthimos ◽  
Holly Dew ◽  
Oliver Smart ◽  
Marie Wiltshire ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Crucial Role ◽  
Cellular Localization ◽  
Texture Features ◽  
Stress Factors ◽  
Adaptation To Hypoxia ◽  
Machine Learning Classification ◽  
Hypoxia Exposure ◽  
Pc3 Cells

Aquaporins are required by cells to enable fast adaptation to volume and osmotic changes, as well as microenvironmental metabolic stimuli. Aquaglyceroporins play a crucial role in supplying cancer cells with glycerol for metabolic needs. Here, we show that AQP3 is differentially expressed in cells of a prostate cancer panel. AQP3 is located at the cell membrane and cytoplasm of LNCaP cell while being exclusively expressed in the cytoplasm of Du145 and PC3 cells. LNCaP cells show enhanced hypoxia growth; Du145 and PC3 cells display stress factors, indicating a crucial role for AQP3 at the plasma membrane in adaptation to hypoxia. Hypoxia, both acute and chronic affected AQP3′s cellular localization. These outcomes were validated using a machine learning classification approach of the three cell lines and of the six normoxic or hypoxic conditions. Classifiers trained on morphological features derived from cytoskeletal and nuclear labeling alongside corresponding texture features could uniquely identify each individual cell line and the corresponding hypoxia exposure. Cytoskeletal features were 70–90% accurate, while nuclear features allowed for 55–70% accuracy. Cellular texture features (73.9% accuracy) were a stronger predictor of the hypoxic load than the AQP3 distribution (60.3%).

scholarly journals The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines. Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 409
Author(s):  
Alicja Chrzanowska ◽  
Wioletta Olejarz ◽  
Grażyna Kubiak-Tomaszewska ◽  
Andrzej K. Ciechanowicz ◽  
Marta Struga
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Cancer Cell Lines ◽  
Lncap Cells ◽  
Ic50 Values ◽  
Late Apoptosis ◽  
Pc3 Cells

Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress.

scholarly journals Chemometrics-Enabled Raman Spectrometric Qualitative Determination and Assessment of Biochemical Alterations during Early Prostate Cancer Proliferation in Model Tissue

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
John I. Githaiga ◽  
Hudson K. Angeyo ◽  
Kenneth A. Kaduki ◽  
Wallace D. Bulimo
Keyword(s):  
Prostate Cancer ◽  
Nucleic Acids ◽  
Raman Spectra ◽  
Cell Lines ◽  
Difference Spectra ◽  
Cancer Proliferation ◽  
Biochemical Alterations ◽  
Pc3 Cells ◽  
Intensity Ratios ◽  
Spectral Intensities

The use of Raman spectroscopy combined with multivariate chemometrics for disease diagnosis has attracted great attention from researchers in recent years. This is because it is a noninvasive and nondestructive detection approach with enhanced sensitivity. However, a major challenge when analyzing spectra from biological samples has been the detection of subtle biochemical alterations buried in background and fluorescence noise. This work reports a qualitative chemometrics-assisted investigation of subtle biochemical alterations associated with prostate malignancy in model biological tissue (metastatic androgen insensitive (PC3) and immortalized normal (PNT1a) prostate cell lines). Raman spectra were acquired from PC3 and PNT1a cells at various stages of growth, and their biochemical alterations were determined from difference spectra between the two cell lines (for prominent alterations) and principal component analysis (PCA) (for subtle alterations). The Raman difference spectra were computed by subtracting the normalized mean spectral intensities of PNT1a cells from the normalized mean spectral intensities of PC3 cells. These difference spectra revealed prominent biochemical alterations associated with the malignant PC3 cells at 566 ± 0.70 cm−1, 630 cm−1, 1370 ± 0.86 cm−1, and 1618 ± 1.73 cm−1 bands. The band intensity ratios at 566 ± 0.70 cm−1 and 630 cm−1 suggested that prostate malignancy can be associated with an increase in relative amounts of nucleic acids and lipids, respectively, whereas those at 1370 ± 0.86 cm−1 and 1618 ± 1.73 cm−1 suggested that prostate malignancy can be associated with a decrease in relative amounts of saccharides and tryptophan, respectively. In the analysis using PCA, intermediate-order and high-order principal components (PCs) were used to extract the subtle biochemical fingerprints associated with the cell lines. This revealed subtle biochemical differences at 1076 cm−1, (1232, 1234 cm−1), (1276, 1278 cm−1), (1330, 1333 cm−1), (1434, 1442 cm−1), and (1471, 1479 cm−1). The band intensity ratios at 1076 cm−1 and 1232 cm−1 suggested that prostate malignancy can be associated with an increase in subtle amounts of nucleic acids and amide III components, respectively. The method reported here has demonstrated that subtle biochemical alterations can be extracted from Raman spectra of normal and malignant cell lines. The identified subtle bands could play an important role in quantitative monitoring of early biomarker alterations associated with prostate cancer proliferation.

scholarly journals EVALUATION OF [11C]MPC-6827 AS A MICROTUBULE TARGETING PET RADIOTRACER IN CANCER CELL LINES

2019 ◽  
pp. 43-47
Author(s):  
J. S. DILEEP KUMAR ◽  
JAYA PRABHAKARAN ◽  
NARESH DAMUKA ◽  
JUSTIN W. HINES ◽  
STEVEN J. KRIDEL ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Specific Binding ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Microtubule Targeting Agents ◽  
Pc3 Cells

Objective: The objective of this study was to evaluate the uptake and specificity of [11C]MPC-6827, a MT targeted PET ligand in prostate, glioblastoma and breast cancer cells. Methods: [11C]MPC-6827 was synthesized by reacting corresponding desmethyl precursors with [11C]CH3I in a GE-FX2MeI/FX2M radiochemistry module. In vitro binding of [11C]MPC-6827 was performed in breast cancer MDA-MB-231, glioblastoma (GBM) patient-derived tumor (GBM-PDX), GBM U251 and prostate cancer 3 (PC3) cell lines at 37 °C in quadruplicate at 5, 15, 30, 60, and 90 minute incubation time. The nonspecific bindings were determined by incubation with unlabeled microtubule targeting agents MPC-6827, HD-800, colchicine, paclitaxel and docetaxel (5.0 mM). Results: [11C]MPC-6827 provided the highest binding in the breast cancer cell, MDA-MB-231, among all the cells studied, with 90% specific binding. [11C]MPC-6827 binds to glioblastoma PDX and U251 cells with ~50% and 40% specific binding, whereas, prostate cancer cell line, PC3 cells showed 40% specific binding. [11C]MPC-6827 also exhibits binding to the taxane and colchicine binding sites of MTs, in MDA-MB-231 cells. Conclusion: These data indicate that [11C]MPC-6827 can be a promising PET radiotracer for preclinical imaging of the brain and peripheral cancers.

scholarly journals Activation of the Y1 Receptor by Neuropeptide Y Regulates the Growth of Prostate Cancer Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1466-1473 ◽  
Author(s):  
Massimiliano Ruscica ◽  
Elena Dozio ◽  
Stéphane Boghossian ◽  
Giorgio Bovo ◽  
Vera Martos Riaño ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuropeptide Y ◽  
Cell Lines ◽  
Y1 Receptor ◽  
Intracellular Signals ◽  
Relevant Role ◽  
Pc3 Cells ◽  
Du145 Cells ◽  
Kinetics Of

This study deals with the role of neuropeptide Y (NPY) in the regulation of cell proliferation. NPY is expressed in the normal and tumoral prostate, but no data on its possible role in prostate cancer (PCa) progression are available. Therefore, we evaluated the direct effect of NPY on the growth of the human PCa cell lines LNCaP (androgen dependent) and DU145 and PC3 (androgen independent). All PCa cell lines expressed Y1-R gene and protein. NPY treatment reduced the proliferation of LNCaP and DU145 cells and increased that of PC3 cells. The Y1-R antagonist BIBP3226 abolished such effects, suggesting a mandatory role of Y1-R in this process. LNCaP cells showed elevated constitutive levels of phosphorylated ERK1/2, which were not affected by NPY. In DU145 cells, NPY stimulated a long-lasting ERK1/2 activation, whereas, in PC3 cells, this effect was rapid and transient and required activation of protein kinase C. Moreover, in both cell lines, pretreatment with BIBP3226 prevented the NPY-induced ERK1/2 phosphorylation, further supporting Y1-R involvement. NPY treatment reduced forskolin-stimulated cAMP accumulation only in PC3 cells and did not change intracellular calcium concentration in any PCa cell line. These data indicate that NPY may directly regulate PCa cell growth via Y1-R. The direction of this effect appears to be related to the time kinetics of MAPK activation, i.e. long-lasting vs. transient, and to the clone-specific involvement of other intracellular signals. These findings suggest that NPY-related mechanisms might play a relevant role in the progression of PCa, at both androgen dependent and independent stages.

Characterization of Dopamine Receptor Associated Drugs on the Proliferation and Apoptosis of Prostate Cancer Cell Lines

2020 ◽  
Vol 20 ◽  
Author(s):  
Fatemeh Akbarian ◽  
Farid Dadkhah ◽  
Arezoo Campbel ◽  
Farrokh Asadi ◽  
Ghasem Ahangari
Keyword(s):  
Prostate Cancer ◽  
Gene Family ◽  
Dopamine Receptor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Therapeutic Effects ◽  
Prostate Cancer Cell Lines ◽  
Pc3 Cells

Background: Dopamine receptor (DR) gene family play an essential role in the regulation of interleukin-6 (IL-6) production. Our prior analysis of human prostate biopsy samples demonstrated the increased expression of IL-6 and a down regulating trend for dopamine receptor gene family. Objective: The objective was to investigate the expression of dopamine receptors, their catabolizing enzyme and IL-6 in prostate cancer cell lines and assess pharmacological effect of dopamine receptor modulators as a novel class of drugs repurposed for treatment of prostate cancer. Methods: The therapeutic effect of dopamine, DR agonists, and DR antagonist were examined using LNCaP and PC3 cell lines.CellviabilityandproliferationwereassessedbyMTTassayandproliferatingcellnuclearantigenexpressionanalysis, respectively. Furthermore, bax/bcl2 ratio, immunofluorescence assay and flow cytometric assay were performed for apoptosis analysis. RT-q PCR analysis was used to characterize relative expression of dopamine-related genes, catabolic enzyme catechol-o-methyl-transferase (COMT) and IL-6 before and after treatment to assess the therapeutic effects of drugs. Results: LNCaP cells express DRD1, DRD2, DRD5 and COMT genes and PC3 cells only express IL-6 gene. In-vitro, dopamine receptor agonists reduced cell viability of LNCaP and PC3 cells. In contrast, dopamine and dopamine receptor antagonist significantly increased tumor growth in PC3 cells. Conclusion: Our results offer novel suggestion for a pathogenic role of dopamine receptor signaling in prostate cancer adenocarcinoma and indicates that modulators of DR-IL-6 pathway, including FDA-approved drug bromocriptine, might be utilized as novel drug repurposing strategy.

scholarly journals Curcumin Nanoparticles and Their Cytotoxicity in Docetaxel-Resistant Castration-Resistant Prostate Cancer Cells

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 253
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Priyanka Prathipati ◽  
Joey Trieu Nguyen ◽  
Evan T. Keller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Drug Loading ◽  
Antioxidant Properties ◽  
Entrapment Efficiency ◽  
Glycol Succinate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Cytotoxicity Studies ◽  
Pc3 Cells

Most prostate cancer patients develop resistance to anti-androgen therapy. This is referred to as castration-resistant prostate cancer (CRPC). Docetaxel (DTX) is the mainstay treatment against CRPC. However, over time patients eventually develop DTX resistance, which is the cause of the cancer-related mortality. Curcumin (CUR) as a natural compound has been shown to have very broad pharmacological activities, e.g., anti-inflammatory and antioxidant properties. However, CUR is very hydrophobic. The objective of this study was to develop CUR nanoparticles (NPs) and evaluate their cytotoxicity in DTX-resistant CRPC cells for the treatment of DTX-resistant CRPC. We tested solubility of CUR in different lipids and surfactants. Finally, Miglyol 812 and D-alpha-tocopheryl poly (ethylene glycol) succinate 1000 (TPGS) were chosen to prepare lipid-based NPs for CUR. We fully characterized CUR NPs that had particle size < 150 nm, high drug loading (7.5%), and entrapment efficiency (90%). Moreover, the CUR NPs were successfully lyophilized without using cryoprotectants. We tested the cytotoxicity of blank NPs, free CUR, and CUR NPs in sensitive DU145 and PC3 cells as well as their matching docetaxel-resistant cells. Cytotoxicity studies showed that blank NPs were very safe for all tested prostate cancer cell lines. Free CUR overcame the resistance in PC3 cells, but not in DU145 cells. In contrast, CUR NPs significantly increased CUR potency in all tested cell lines. Importantly, CUR NPs completely restored CUR potency in both resistant DU145 and PC3 cells. These results demonstrate that the CUR NPs have potential to overcome DTX resistance in CRPC.

The Effect of EGFR-Related Tyrosine Kinase Activity Inhibition on the Growth and Invasion Mechanisms of Prostate Carcinoma Cell Lines

2003 ◽  
Vol 18 (2) ◽  
pp. 139-146 ◽  
Author(s):  
A. Ünlü ◽  
R.E. Leake
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Kinase Activity ◽  
Cell Types ◽  
Tyrosine Kinase Activity ◽  
Matrigel Invasion ◽  
Pc3 Cells ◽  
Epidermal Growth

Increased urokinase plasminogen activator (uPA) levels and epidermal growth factor receptor (EGFR)-related tyrosine kinase activity are associated with poor prognosis in several cancers. We studied the effect of epidermal growth factor (EGF) and a specific inhibitor of EGFR, ZM252868, on the growth and invasiveness of the prostate cancer cell lines PC3 and DU145. PC3 cell growth was stimulated by exogenous EGF but DU145 cell growth was not. EGFR-specific tyrosine kinase inhibitor significantly inhibited the growth of both cell types. EGF increased uPA protein level and uPA activity in both cell types. EGF stimulation also resulted in increased uPAR transcript in both cell lines. uPA production and activity were suppressed by the inhibitor to well below the levels in control cells. Matrigel invasion of PC3 cells was increased by EGF. ZM252868 also reversed the EGF-stimulated matrigel invasion by PC3 cells. Our results indicate that EGF is a potent stimulative agent for both growth and invasion in prostate cancer cells, and that targeting the EGFR function inhibits not only tumor growth but also invasiveness.

scholarly journals Selenium Biomarkers in Prostate Cancer Cell Lines and Influence of Selenium on Invasive Potential of PC3 Cells

2013 ◽  
Vol 3 ◽  
Author(s):  
Wouter Hendrickx ◽  
Julie Decock ◽  
Francis Mulholland ◽  
Yongping Bao ◽  
Susan Fairweather-Tait
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Invasive Potential ◽  
Prostate Cancer Cell Lines ◽  
Pc3 Cells

scholarly journals Biological Potential and Mechanism of Prodigiosin from Serratia marcescens Subsp. lawsoniana in Human Choriocarcinoma and Prostate Cancer Cell Lines

2018 ◽  
Vol 19 (11) ◽  
pp. 3465 ◽  
Author(s):  
Dan Li ◽  
Jun Liu ◽  
Xin Wang ◽  
Di Kong ◽  
Wei Du ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Serratia Marcescens ◽  
Cell Lines ◽  
Prostate Cancer Cell ◽  
Red Pigment ◽  
Anticancer Activities ◽  
Prostate Cancer Cell Lines ◽  
Pc3 Cells

Tripyrrole molecules have received renewed attention due to reports of numerous biological activities, including antifungal, antibacterial, antiprotozoal, antimalarial, immunosuppressive, and anticancer activities. In a screen of bacterial strains with known toxicities to termites, a red pigment-producing strain, HDZK-BYSB107, was isolated from Chamaecyparis lawsoniana, which grows in Oregon, USA. Strain HDZK-BYSB107 was identified as Serratia marcescens subsp. lawsoniana. The red pigment was identified as prodigiosin using ultraviolet absorption, LC-MS, and 1H-NMR spectroscopy. The bacterial prodigiosin had an inhibitory effect on both Gram-negative and Gram-positive bacteria. The main objective of this study was to explore the anticancer activities and mechanism of strain HDZK-BYSB107 prodigiosin by using human choriocarcinoma (JEG3) and prostate cancer cell lines (PC3) in vitro and JEG3 and PC3 tumor-bearing nude mice in vivo. In vitro anticancer activities showed that the bacterial prodigiosin induced apoptosis in JEG3 cells. In vivo anticancer activities indicated that the prodigiosin significantly inhibited the growth of JEG3 and PC3 cells, and the inhibitory activity was dose and time dependent. The anticancer efficacy of the bacterial prodigiosin on JEG3 and PC3 cells, JEG3 and PC3 tumor exhibited a correlation with the down regulation of the inhibitor of IAP family, including XIAP, cIAP-1 and cIAP-2, and the activation of caspase-9 and caspase-3 accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. The expressions of P53 and Bax/Bcl-2 in JEG3 and PC3 cells were significantly higher than in untreated groups. Our results indicated that the bacterial prodigiosin extracted from C. lawsoniana is a promising molecule due to its potential for therapeutic applications.

scholarly journals Repurposing FDA approved drugs as radiosensitizers for treating hypoxic prostate cancer

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Becky A. S. Bibby ◽  
Niluja Thiruthaneeswaran ◽  
Lingjian Yang ◽  
Ronnie R. Pereira ◽  
Elisabet More ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Poor Prognostic Factor ◽  
Connectivity Mapping ◽  
Mapping Software ◽  
Sulforhodamine B Assay ◽  
Pc3 Cells ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Background The presence of hypoxia is a poor prognostic factor in prostate cancer and the hypoxic tumor microenvironment promotes radioresistance. There is potential for drug radiotherapy combinations to improve the therapeutic ratio. We aimed to investigate whether hypoxia-associated genes could be used to identify FDA approved drugs for repurposing for the treatment of hypoxic prostate cancer. Methods Hypoxia associated genes were identified and used in the connectivity mapping software QUADrATIC to identify FDA approved drugs as candidates for repurposing. Drugs identified were tested in vitro in prostate cancer cell lines (DU145, PC3, LNCAP). Cytotoxicity was investigated using the sulforhodamine B assay and radiosensitization using a clonogenic assay in normoxia and hypoxia. Results Menadione and gemcitabine had similar cytotoxicity in normoxia and hypoxia in all three cell lines. In DU145 cells, the radiation sensitizer enhancement ratio (SER) of menadione was 1.02 in normoxia and 1.15 in hypoxia. The SER of gemcitabine was 1.27 in normoxia and 1.09 in hypoxia. No radiosensitization was seen in PC3 cells. Conclusion Connectivity mapping can identify FDA approved drugs for potential repurposing that are linked to a radiobiologically relevant phenotype. Gemcitabine and menadione could be further investigated as potential radiosensitizers in prostate cancer.

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