scholarly journals Specifically Binding of D-Amino Neuraminic Acid to Ganglioside Studied in Prostate Cancer Cells

2021 ◽  
Author(s):  
Kenan Demir ◽  
Huseyin Aktug ◽  
Gurkan Yigitturk ◽  
Eda Acikgoz ◽  
Gunnur Guler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Enzyme Inhibitor ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Cell Group ◽  
Synthesis Inhibitor ◽  
Cell Groups ◽  
Negative Effect ◽  
Synthase Inhibitor

Abstract Aims: The aim of this study was to investigate the cellular binding site of human KDN (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid). The KDN molecule is a member of the sialic acid family, and its expression increases in cancer cells. Although KDN has been shown to bind to GM3 (Monosialodihexosyl Ganglioside) in trout sperm.Methods and Results: Prostate cancer cell line (DU145) was used in this study. Each experimental group was divided into 3 groups: control, GCS (Glucosylceramide synthase) enzyme inhibitor Genz-123346 treated, and GM3 synthesis inhibitor Triptolide treated. Each group was stained using the immunocytochemical method for GM3, GD3 (Disialosyllactosylceramide) and KDN. The FTIR (Fourier Transform Infrared Spectroscopy) analysis was performed to elucidate the cellular changes upon treatment. The non-treated number 1 cell group stained positive with all of GM3, GD3 and KDN, the GCS enzyme blocked with Genz-123346 number 2 cell groups stained positive with only KDN. Furthermore, GD3 Synthase inhibitor Triptolide treated number 3 cell group stained positive with GM3 and KDN. Measurements with FTIR showed apoptotic features with Triptolide while Genz-123346 had no negative effect on the cell viability. The decrease in sugar constructions was revealed and the results that we obtained with staining were reinforced.Conclusions: Determining the location of bounded KDN is important in selecting new targets for cancer treatment researches. It has been shown that KDN is not inhibited by both GM3 inhibition and GD3 inhibition, and thus, KDN might also bind to different places, be specific, and not only attached to any of gangliosides of the GM or GD series.

scholarly journals Superoxide Dismutase 1 Regulation of CXCR4-Mediated Signaling in Prostate Cancer Cells is Dependent on Cellular Oxidative State

2015 ◽  
Vol 37 (6) ◽  
pp. 2071-2084 ◽  
Author(s):  
Brent Young ◽  
Chad Purcell ◽  
Yi-Qun Kuang ◽  
Nicholle Charette ◽  
Denis J. Dupré
Keyword(s):  
Prostate Cancer ◽  
Superoxide Dismutase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Direct Interaction ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Cell Types ◽  
Intracellular Loop

Background/Aims: CXCL12, acting via one of its G protein-coupled receptors, CXCR4, is a chemoattractant for a broad range of cell types, including several types of cancer cells. Elevated expression of CXCR4, and its ligand CXCL12, play important roles in promoting cancer metastasis. Cancer cells have the potential for rapid and unlimited growth in an area that may have restricted blood supply, as oxidative stress is a common feature of solid tumors. Recent studies have reported that enhanced expression of cytosolic superoxide dismutase (SOD1), a critical enzyme responsible for regulation of superoxide radicals, may increase the aggressive and invasive potential of malignant cells in some cancers. Methods: We used a variety of biochemical approaches and a prostate cancer cell line to study the effects of SOD1 on CXCR4 signaling. Results: Here, we report a direct interaction between SOD1 and CXCR4. We showed that SOD1 interacts directly with the first intracellular loop (ICL1) of CXCR4 and that the CXCL12/CXCR4-mediated regulation of AKT activation, apoptosis and cell migration in prostate cancer (PCa) cells is differentially modulated under normal versus hypoxic conditions when SOD1 is present. Conclusions: This study highlights a potential new regulatory mechanism by which a sensor of the oxidative environment could directly regulate signal transduction of a receptor involved in cancer cell survival and migration.

Carvacrol Induced Program Cell Death and Cell Cycle Arrest in Androgen-Independent Human Prostate Cancer Cells via Inhibition of Notch Signaling

2019 ◽  
Vol 19 (13) ◽  
pp. 1588-1608 ◽  
Author(s):  
Fahad Khan ◽  
Vipendra K. Singh ◽  
Mohd Saeed ◽  
Mohd A. Kausar ◽  
Irfan A. Ansari
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Prostate Cancer Cell Line ◽  
Prostate Cancer Cells ◽  
Annexin V Assay

Background: Several studies have revealed that abnormal activation of Notch signaling is closely related with the development and progression of prostate cancer. Although there are numerous therapeutic strategies, a more effective modality with least side effects is urgently required for the treatment of prostate cancer. Carvacrol is a monoterpenoid phenol and majorly present in the essential oils of Lamiaceae family plants. Many previous reports have shown various biological activities of carvacrol like antioxidant, antiinflammatory and anticancer properties. Recently, we have shown potent anticancer property of carvacrol against prostate cancer cell line DU145. In the current study, we report the chemopreventive and therapeutic potential of carvacrol against another prostate cancer cell line PC-3 with its detailed mechanism of action. Methods: To determine the effect of the carvacrol on prostate cancer cells, the cell viability was estimated by MTT assay and cell death was estimated by LDH release assay. The apoptotic assay was performed by DAPI staining and FITC-Annexin V assay. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Cell cycle analysis was performed by flow cytometry. Gene expression analysis was performed by quantitative real time PCR. Results: Our results suggested that the carvacrol treatment significantly reduced the cell viability of PC-3 cells in a dose- and time-dependent manner. The antiproliferative action of carvacrol was correlated with apoptosis which was confirmed by nuclear condensation, FITC-Annexin V assay, modulation in expression of Bax, Bcl-2 and caspase activation. The mechanistic insight into carvacrol-induced apoptosis leads to finding of elevated level of Reactive Oxygen Species (ROS) and mitochondrial membrane potential disruption. Cell cycle analysis revealed that carvacrol prevented cell cycle in G0/G1 that was associated with decline in expression of cyclin D1 and Cyclin-Dependent Kinase 4 (CDK4) and augmented expression of CDK inhibitor p21. Having been said the role of hyperactivation of Notch signaling in prostate cancer, we also deciphered that carvacrol could inhibit Notch signaling in PC-3 cells via downregulation of Notch-1, and Jagged-1. Conclusion: Thus, our previous and current findings have established the strong potential of carvacrol as a chemopreventive agent against androgen-independent human prostate cancer cells.

Androgen-dependent regulation of Her-2/neu in prostate cancer cells

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10099-10099
Author(s):  
R. Berger ◽  
D. I. Lin ◽  
M. Nieto ◽  
S. Signoretti ◽  
W. C. Hahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Prostate Cancer Cells ◽  
In Vivo Experiments ◽  
Her 2

10099 Background: The mechanisms underlying the progression of prostate cancer to androgen independence remain poorly understood. Overexpression of Her-2/neu (c-ErbB2) activates the androgen receptor pathway and confers a survival and growth advantage to prostate cancer cells in an androgen-deficient milieu. Methods: Androgen-sensitive prostate cancer cell line LNCaP was used as a model system in vitro and in vivo. Experiments in mice were undertaken by injecting cells orthotopically into the ventral lobe of the mice prostate. Results: Here, we report that androgen receptor (AR) and Her-2/neu reciprocally regulate each other in LNCaP human prostate cancer cells. Absence of androgens, AR blockade with Casodex (bicalutamide) or suppression of AR with RNAi induced Her-2/neu protein expression and phosphorylation in vitro and in vivo. Similarly, suppression of Her-2-neu expression resulted in AR upregulation. In contrast, upon re-administration of androgens, Her-2/neu mRNA, protein and phosphorylation levels decreased linearly with increasing concentrations of androgens as LNCaP cells re-entered the cell cycle. Conclusions: Thus, induction and activation of Her-2/neu occurs in an androgen-depleted environment or as a result of AR inactivation, promoting androgen-independent survival of prostate cancer cells. No significant financial relationships to disclose.

scholarly journals Co-downregulation of GRP78 and GRP94 induces apoptosis and inhibits migration in prostate cancer cells

2019 ◽  
Vol 14 (1) ◽  
pp. 384-391 ◽  
Author(s):  
Tong Lu ◽  
Yue Wang ◽  
Kang Xu ◽  
Zhijun Zhou ◽  
Juan Gong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Small Interfering Rnas ◽  
Prostate Cancer Cells ◽  
Vimentin Expression ◽  
Expression Levels ◽  
Glucose Regulated Protein

AbstractBackgroundBoth glucose-regulated protein 78 kDa (GRP78) and glucose-regulated protein 94 kDa (GRP94) are important molecular chaperones that play critical roles in maintaining tumor survival and progression. This study investigated the effects in prostate cancer cells following the downregulation of GRP78 and GRP94.MethodsRNA interference was used to downregulate GRP78 and GRP94 expression in the prostate cancer cell line, PC-3. The effects on apoptosis and cell migration was examined along with expression of these related proteins.ResultsSmall interfering RNAs targeting GRP78 and GRP94 successfully down-regulated their expression. This resulted in the induction of apoptosis and inhibition of cell migration. Preliminary mechanistic studies indicated that caspase-9 (cleaved) and Bax expression levels were upregulated while Bcl-2 and vimentin expression levels were downregulated.ConclusionCo-downregulation of GRP78 and GRP94 expression induces apoptosis and inhibits migration in prostate cancer cells.

scholarly journals Implication of β2-adrenergic receptor and miR-196a correlation in neurite outgrowth of LNCaP prostate cancer cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253828
Author(s):  
Ilaria Guerriero ◽  
Håkon Ramberg ◽  
Krizia Sagini ◽  
Manuel Ramirez-Garrastacho ◽  
Kristin A. Taskén ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Adrenergic Receptor ◽  
Neuroendocrine Differentiation ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Prostate Cancer Cells ◽  
Β2 Adrenergic Receptor ◽  
Low Levels ◽  
Androgen Depletion

The β2-adrenergic receptor has been shown to be involved in neuroendocrine differentiation and to contribute to the development of aggressive prostate cancer. In this study we have investigated whether miR-196a plays a role in the regulation of the β2-adrenergic receptor in the LNCaP prostate cancer cell line. Our results show that the expression of miR-196a is elevated in LNCaP prostate cancer cells with reduced levels of β2-adrenergic receptor after stably transfection with three different shRNAs. Furthermore, treatment with β-blockers showed that this upregulation is strictly related to the low levels of β2-adrenergic receptor and not to the inhibition of the receptor signaling activity. Finally, we found that the reduced ability of LNCaP cells with low levels of β2-adrenergic receptor to initiate neuroendocrine differentiation under androgen depletion conditions is mediated by miR-196a. In conclusion, this study provides the rational for a role of miR-196a in the β2-adrenergic receptor mediated neuroendocrine differentiation of LNCaP prostate cancer cells.

scholarly journals SAT-LB9 Anti-Cancer Properties of RISUG Against Prostrate Cancer Cell Line PC-3 -Invitro Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pankaj Singroul ◽  
Palak Singh ◽  
Sujoy K Guha ◽  
Surabhi Gupta ◽  
Pradeep Kumar Chaturvedi
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Viable Cells ◽  
Anti Cancer ◽  
The Media

Abstract Cancer cell lines were initially established for understanding the genetic, functional, and epigenetic properties of cancer cells. The PC3 cell line is a human-derived prostate cancer cell line from the metastatic bone site of the grade IV adenocarcinoma patient. With the invention of RISUG-a polymeric male contraceptive, and studying its astonishing properties such as anti-microbial activity, there have been multiple hypotheses stating its anti-cancerous effect based on its physical and chemical nature[1]. This study focuses on understanding the effect of RISUG on prostate cancer cell line PC3 via MTT assay.For our study, 10 mg/ml working concentration of RISUG in DMSO (solvent) was used for the treatment to the cells. The dosage given to the cells for three varying incubation periods of 24 hours, 48 hours and 72 hours were analyzed for there viable cells post treatment. The dose was delivered with the media such that the final concentration of DMSO in the media is 1.5% (optimized) to avoid vehicle toxicity. The MTT assay was employed to study the cytotoxicity effect by measuring the amount of viable cells post treatment. The observations were statistically significant for the anti-cancerous effect of RISUG on PC3 prostate cancer cells for 72 hours, the optimized minimum incubation time/ time of action for RISUG to exhibit significant anti-cancer effect against PC3 cells. However, further in depth research is necessary for the understanding of the mechanism behind these actions. Keywords: RISUG, Prostate Cancer, DMSO, Cell line, Reference: 1. Subramanian, B., Agarwal, T., Basak, P., Maiti, T., & Guha, S. (2019). RISUG® based improved intrauterine contraceptive device (IIUCD) could impart protective effects against development of endometrial cancer. Medical Hypotheses, 124, 67-71. doi: 10.1016/j.mehy.2019.02.026

scholarly journals Preprocessing Tools Applied to Improve the Assessment of Aldrin Effects on Prostate Cancer Cells Using Raman Spectroscopy

2017 ◽  
Vol 72 (3) ◽  
pp. 489-500 ◽  
Author(s):  
Víctor Olmos ◽  
Carmen Bedia ◽  
Romà Tauler ◽  
Anna de Juan
Keyword(s):  
Prostate Cancer ◽  
Raman Spectroscopy ◽  
Discriminant Analysis ◽  
Least Squares ◽  
Cancer Cells ◽  
Partial Least Squares ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Environmental Response ◽  
Prostate Cancer Cells

The study of pollutant effects on living organisms provides information about the possible biological and environmental response to a contaminant. Progression of prostate cancer may be related to exposure to pesticides or other chemical substances. In this work, the effect of the pesticide aldrin on human prostate cancer cells (DU145) is studied using Raman spectroscopy and chemometric techniques. Prostate cancer cell line DU145 has been exposed acutely the pesticide aldrin. Individual Raman spectra coming from control and treated cell populations have been acquired. Partial least squares discriminant analysis (PLSDA) has been used to assess differences among treated and control samples and to identify spectral biomarkers associated with pollutant stress. Some preprocessing methodologies have been tested in order to improve the capability of discrimination between fingerprints. Partial least squares discriminant analysis results suggest that the best normalization–scaling preprocessing combination is provided by Euclidean normalization (EN)-SIMPLISMA-based scaling (SBS). SIMPLISMA-based scaling has been proposed as a scaling method focused on the classification objective, which enhances variables with high relative variation among samples. The most relevant spectral variables related to aldrin effect on DU145 seem to be mainly related to lipids, proteins, and variations in nucleic acids.

scholarly journals Membrane Interactome of a Recombinant Fragment of Human Surfactant Protein D Reveals GRP78 as a Novel Binding Partner in PC3, a Metastatic Prostate Cancer Cell Line

2021 ◽  
Vol 11 ◽  
Author(s):  
Gargi Thakur ◽  
Gajanan Sathe ◽  
Indra Kundu ◽  
Barnali Biswas ◽  
Poonam Gautam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Recombinant Fragment ◽  
Binding Partner

Surfactant protein-D (SP-D), a member of the collectin family has been shown to induce apoptosis in cancer cells. SP-D is composed of an N-terminal collagen-like domain and a calcium-dependent carbohydrate recognition domain (CRD). Recently, we reported that a recombinant fragment of human SP-D (rfhSP-D), composed of homotrimeric CRD region, induced intrinsic apoptotic pathway in prostate cancer cells. Here, we analyzed the membrane interactome of rfhSP-D in an androgen-independent prostate cancer cell line, PC3, by high resolution mass spectrometry and identified 347 proteins. Computational analysis of PPI network of this interactome in the context of prostate cancer metastasis and apoptosis revealed Glucose Regulated Protein of 78 kDa (GRP78) as an important binding partner of rfhSP-D. Docking studies suggested that rfhSP-D (CRD) bound to the substrate-binding domain of glycosylated GRP78. This was further supported by the observations that human recombinant GRP78 interfered with the binding of rfhSP-D to anti-SP-D polyclonal antibodies; GRP78 also significantly inhibited the binding of recombinant full-length human SP-D with a monoclonal antibody specific to the CRD in a dose-dependent manner. We conclude that the interaction with rfhSP-D is likely to interfere with the pro-survival signaling of GRP78.

scholarly journals Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Fangzhen Cai ◽  
Yanmei Zhang ◽  
Jianwei Li ◽  
Sihuai Huang ◽  
Ruilin Gao
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Mtor Pathway ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Apoptotic Pathway ◽  
Proliferation And Metastasis ◽  
Androgen Independent

Abstract The present study investigated the effects of Isorhamnetin on two types of prostate cancer cells (androgen-independent and androgen-dependent) and explored its possible mechanisms underlying such effects. Treatment with Isorhamnetin significantly inhibited cell growth and induced lactate dehydrogenase (LDH) release of androgen-independent DU145 and PC3 prostate cancer cells, but exhibited almost no toxicity effect on androgen-dependent LNCaP prostate cancer cell line or normal human prostate epithelial PrEC cells, which was achieved by the induction of apoptosis in a mitochondrion-dependent intrinsic apoptotic pathway. Furthermore, Isorhamnetin inhibited cell migration and invasion in concentration-dependent manners by enhancing mesenchymal−epithelial transition (MET) and inhibiting matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9 overexpression. In addition, Isorhamnetin also down-regulated the expression of phosphorylated PI3K (p-P13K), Akt (p-Akt), and mTOR (p-mTOR) proteins in both cancer cells, revealing Isorhamnetin to be a selective PI3K–Akt–mTOR pathway inhibitor. In summary, these findings propose that Isorhamnetin might be a novel therapeutic candidate for the treatment of androgen-independent prostate cancer.

scholarly journals Proteotranscriptomic Measurements of E6-Associated Protein (E6AP) Targets in DU145 Prostate Cancer Cells

2018 ◽  
Vol 17 (6) ◽  
pp. 1170-1183 ◽  
Author(s):  
Twishi Gulati ◽  
Cheng Huang ◽  
Franco Caramia ◽  
Dinesh Raghu ◽  
Piotr J. Paul ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Proteomic Approach

Prostate cancer is a common cause of cancer-related death in men. E6AP (E6-Associated Protein), an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumor suppressor targets of E6AP, promyelocytic leukemia protein and p27. To explore additional players that are regulated downstream of E6AP, we combined a transcriptomic and proteomic approach. We identified and quantified 16,130 transcripts and 7,209 proteins in castration resistant prostate cancer cell line, DU145. A total of 2,763 transcripts and 308 proteins were significantly altered on knockdown of E6AP. Pathway analyses supported the known phenotypic effects of E6AP knockdown in prostate cancer cells and in parallel exposed novel potential links of E6AP with cancer metabolism, DNA damage repair and immune response. Changes in expression of the top candidates were confirmed using real-time polymerase chain reaction. Of these, clusterin, a stress-induced chaperone protein, commonly deregulated in prostate cancer, was pursued further. Knockdown of E6AP resulted in increased clusterin transcript and protein levels in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP. Overall, results from this study provide insight into the potential biological pathways controlled by E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP.

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