scholarly journals Zoledronic Acid Elicits Proinflammatory Cytokine Profile in Osteolytic Prostate Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Chia Lin ◽  
Po-Cheng Liao ◽  
Te-Fu Tsai ◽  
Kuang-Yu Chou ◽  
Hung-En Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Prostate Cancer Cell ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Low Concentrations ◽  
Pc3 Cells ◽  
Inflammatory Profile

Zoledronic acid (ZA), a bisphosphonate used to prevent skeletal fractures in patients with cancers, was demonstrated to induce apoptosis in a number of cancer cells. Our previous study showed that ZA also induces autophagic cell death in metastatic prostate cancer cells. However, the clinical trials using ZA in the treatment of metastatic prostate cancer did not have a longer diseases-free period. Since most of ZA was attracted to the bone after administration, we hypothesized that local prostate cancer cells may evolve prosurvival pathways upon low concentration of ZA treatment. In this study, we investigated the inflammatory effects of ZA on osteolytic PC3 prostate cancer cell, since inflammation was reported to be related to cancer development and survival. Exposure of PC3 cells to various concentrations of ZA resulted in induction of apoptosis and autophagy. The expression of inflammatory biomarkers including interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), and NF-κB was remarkably upregulated in response to ZA treatment in a dose- and time-dependent manner. The production of IL-6 was elevated upon ZA treatment. The antiapoptotic protein Bcl2 was increased with parallel increased level of IL-6. Our data suggest that treatment with low concentrations of ZA enhances the inflammatory profile and may serve as a prosurvival signaling pathway in PC3 cells.

scholarly journals ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro

2020 ◽  
Vol 19 ◽  
pp. 153303382094806
Author(s):  
Guangxing Tan ◽  
Lin Jiang ◽  
Gangqin Li ◽  
Kuan Bai
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Nude Mouse ◽  
Luciferase Reporter ◽  
Control Group ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Mouse Xenograft Model ◽  
Pc3 Cells ◽  
Du145 Cells

Objective: To explore the effect and the related mechanism of STAT3 inhibitor AG-490 on inhibiting the proliferation of prostate cancer cells. Methods: PC3 cells and DU145 cells were cultured stably and treated with AG-490 to detect the changes in the activity of PC3 cells and DU145 cells. Thirty 6-8 weeks male BALB/c nude mouse were randomly divided into a control group, a DMSO group, and an AG-490 group to detect differences in various indexes . Results: The overexpression of miR-503-5p depends on the activation of STAT3. After treatment with AG-490, The proliferation and invasion of PC3 cells and DU145 cells and the expression of miR-503-5p were all reduced. Luciferase reporter assay demonstrated that the target proteins of miR-503-5p include PDCD4, TIMP-3, and PTEN. After treatment with AG-490, the expression of PDCD4, TIMP-3, and PTEN in cells was significantly up-regulated. IL-6-induced overexpression of miR-503-5p and restored the expression of STAT3, demonstrating the correlation between STAT3 and miR-503-5p. AG-490 can inhibit tumor growth and induce tumor cell apoptosis in the PC3 BALB/c nude mouse xenograft model. Western blotting and immunohistochemical staining showed that the expression levels of STAT3, Ki67, Bcl-2 and MMP-2 in the AG-490 group were significantly reduced, and the expression of PDCD4, TIMP-3 and PTEN increased. Conclusion: AG-490 can inhibit the growth of prostate cancer cells in a miR-503-5p-dependent manner by targeting STAT3. AG-490 is expected to become a new candidate drug for the treatment of prostate cancer.

scholarly journals Cisplatin and Paclitaxel Modulated the Cell Survival Potential of Prostate Cancer Cells

Proceedings ◽  
2020 ◽  
Vol 40 (1) ◽  
pp. 42
Author(s):  
Kashani ◽  
Kilbas ◽  
Yerlikaya ◽  
Gurkan ◽  
Arisan
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Cell Viability Assay ◽  
Chemotherapy Drugs

Prostate cancer is the second common cause of death among men worldwide. In the treatment of prostate cancer, conventional chemotherapeutics are commonly used. The plant alkaloid Paclitaxel and platinum-based cisplatin are the most common chemotherapy drugs. The transcription factor p53 has a potential target in the regulation of cell response to DNA damage of prostate cancer. Although the effectiveness of these drugs on prostate cancer cell progression had been proved, the mechanistic action of these drugs on the progression of the disease is not detailed explained. In this study, we aim to examine the function of p53 overexpression in prostate cancer cell survival. Therefore, we treated wild type (wt) and p53 overexpressed PC3 (p53+) prostate cancer cells with cisplatin or paclitaxel. According to the MTT Cell Viability assay, cisplatin (12.5–25–50 µM) was found to be more effective decreasing PC3 and PC3 p53+ cell viability in a dose-dependent manner compared to paclitaxel (12.5–25–50 nM). Colony formation assay showed that treatment of cells with cisplatin or paclitaxel caused the loss of colony forming ability of PC3 and PC3 p53+ cells. In addition, the critical apoptotic markers Caspase-3 and Caspase-9 expressions were altered with cisplatin or paclitaxel treated PC3 wt and p53+ cells.

scholarly journals Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jeremy J. McGuire ◽  
Jeremy S. Frieling ◽  
Chen Hao Lo ◽  
Tao Li ◽  
Ayaz Muhammad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Prostate Cancer Cell ◽  
Prostate Cancer Cells ◽  
Interleukin 28 ◽  
Selection Of

AbstractBone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.

scholarly journals LncRNA DANCR Restrains Sensitivity to 5-fluorouracil in Prostate Cancer through Sponging MiR-577

2021 ◽  
Vol 21 (04) ◽  
Author(s):  
Minghua Zhang
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Prostate Cancer Cell ◽  
Luciferase Reporter ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Prostate Cancer Cell Lines ◽  
Pc3 Cells

ABSTRACT This present study explored the functions of lncRNA DANCR on regulating sensitivity to 5-fluorouracil (5- FU) in prostate cancer in vitro. The RT-qPCR examined RNA expressions of LNCRNA DANCR in RWPE-1, VCaP, PC3 and LNCaP cells, which also measured RNA levels of miR-577 in PC3 cells. DANCR was highly expressed in prostate cancer cell lines. 5-FU (0, 1, 5 and 10¼M) treatment induced the decrease of PC3 cell viability and low RNA expressions of DANCR but increased miR-577 in PC3 cells. The luciferase reporter test detected the binding between DNACR and miR- 577 . Interactions between DANCR and miR-577 were examined. Knockdown of DANCR downregulated DANCR and Bcl- 2 RNA expressions but accelerated cell viability and upregulated Bax, which were enhanced by the overexpression of miR- 577. Hence, DANCR might restrain sensitivity of prostate cancer cells to 5-FU by downregulating miR-577

Association of cross-talk between α1D-adrenergic receptor (α1D -AR) and transient receptor potential vanilloid 1 (TRPV1) with the proliferation of PC3 prostate cancer cells.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 87-87
Author(s):  
Giorgio Santoni ◽  
Valerio Farfariello ◽  
Maria Beatrice Morelli ◽  
Sonia Liberati ◽  
Massimo Nabissi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cross Talk ◽  
Calcium Influx ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Proton Release ◽  
Trpv1 Receptors ◽  
Pc3 Cells

87 Background: Growing evidence supports the role of α1-ARs in the direct mitogenic effect of catecholamines on prostate cancer (PC) cell growth. The expression of α1D-AR on PC3 prostate cancer cells and the ability of noradrenalin (NA) to stimulate PC3 cell proliferation in a α1D-AR-dependent manner were reported (Quaglia et al., 2005). In addition, TRPV1 expression was also found in prostate cancers (Sanchez et al., 2006). Aim of this study was to investigate the relationship between α1D-AR and TRPV1 receptors and the involvement of TRPV1 in NA-induced proliferation in PC3 cells. Methods: By western blot analysis and confocal microscopy the expression α1D-AR and TRPV1 and localization in PC3 cells were evaluated. PC3 cells were incubated with NA alone or in combination with WS433 and capsazepine (CPZ), α1D-AR and TRPV1 antagonists. Proton release, calcium influx and cell proliferation were assessed in α1D-AR-, TRPV1- or α1D-AR/TRPV1 double-silenced PC3 cells by cytosensor and cytofluorymetric analyses. Finally, lysates from NA-treated PC3 cells alone or in combination with WS433 or CPZ were blotted with anti-phospho ERK, anti-ERK and anti-phospho-(Ser) PKC substrate Abs and Inositol-1,4,5-trisphosphate [3H] radioreceptor assay were performed. Results: α1D-AR and TRPV1 co-localize and are co-immunoprecipitated in PC3 cells. Treatment of PC3 cells with NA strongly stimulated proton release, calcium influx and cell proliferation that were reverted by α1D-AR WS433 and TRPV1 antagonist. NA-induced increase of survival and proliferation was totally abrogated in α1D-AR/TRPV1 silenced cells. In addition, NA stimulates ERK and PKC substrate phosphorylation that was inhibited by WS433 and CPZ. Finally, CPZ treatment inhibited NA-dependent PLC activation, while WS433 had no effect. Conclusions: A functional and structural cross-talk between α1D-AR and TRPV1 receptors control NA-induced proliferation of PC cells. These data strongly suggest the development of new pharmaceutical approaches based on bifunctional antibodies and molecules recognizing both α1D-AR and TRPV1 receptors.

Simvastatin reduces the production of prothrombotic prostasomes in human prostate cancer cells

2008 ◽  
Vol 100 (10) ◽  
pp. 655-662 ◽  
Author(s):  
Matilda Johnell ◽  
Malin Wickström ◽  
Anna Widunder ◽  
Agneta Siegbahn ◽  
Mikael Åberg
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Cholesterol Depletion ◽  
Prostate Cancer Cells ◽  
Prothrombotic State ◽  
Low Concentrations ◽  
Pc3 Cells

SummaryCancer confers a prothrombotic state and statins are associated with a lowered risk for prostate cancer in vivo by unknown mechanisms. Prostate cancer cells release tissue factor (TF)-bearing, cholesterol-rich prostasomes which are procoagulant in vitro and a possible source for the blood-borne TF found in prostate cancer patients. We investigated the effect of cholesterol depletion on the production of prostasomes and on the TF activity in the conditioned medium of simvastatin-treated PC3 cells. Human PC3 prostate cancer cells were treated with high and low concentrations of simvastatin for different time periods. Caspase-3 was detected with the Array Scan microscope, where-asTF mRNA and protein were analyzed by TaqMan and flow cytometry. TF activity was assessed by measuring the cleavage of a chromogenic thrombin substrate. Prostasomes were isolated by repeated centrifugations and detected and quantified by flow cy tometry. A micromolar dose of simvastatin caused reduction of TF expression and induction of apoptosis in the PC3 cells. The levels of TF on the prostasomes were also decreased but the TF activity in the conditioned medium of the simvastatin-treated PC3 cells was increased due to apoptosis-dependent release of prostasomes. Treatment with a nanomolar dose of simvastatin did not induce apoptosis or alter the expression of TF but instead decreased the production and release of the prostasomes. The TF activity was reduced in parity with the decline in prostasome release. In conclusion, in prostate cancer, a nanomolar dose of simvastatin may have an anti-thrombotic effect due to decreased levels of circulating TF-bearing prostasomes.

scholarly journals Cytostatic Action of Novel Histone Deacetylase Inhibitors in Androgen Receptor-Null Prostate Cancer Cells

2021 ◽  
Vol 14 (2) ◽  
pp. 103
Author(s):  
Zohaib Rana ◽  
Joel D. A. Tyndall ◽  
Muhammad Hanif ◽  
Christian G. Hartinger ◽  
Rhonda J. Rosengren
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Hdac Inhibitors ◽  
G1 Arrest ◽  
Prostate Cancer Cells ◽  
Prostate Tumors ◽  
Normal Prostate ◽  
Pc3 Cells ◽  
Du145 Cells

Androgen receptor (AR)-null prostate tumors have been observed in 11–24% of patients. Histone deacetylases (HDACs) are overexpressed in prostate tumors. Therefore, HDAC inhibitors (Jazz90 and Jazz167) were examined in AR-null prostate cancer cell lines (PC3 and DU145). Both Jazz90 and Jazz167 inhibited the growth of PC3 and DU145 cells. Jazz90 and Jazz167 were more active in PC3 cells and DU145 cells in comparison to normal prostate cells (PNT1A) and showed a 2.45- and 1.30-fold selectivity and higher cytotoxicity toward DU145 cells, respectively. Jazz90 and Jazz167 reduced HDAC activity by ~60% at 50 nM in PC3 lysates. At 4 μM, Jazz90 and Jazz167 increased acetylation in PC3 cells by 6- to 8-fold. Flow cytometry studies on the cell phase distribution demonstrated that Jazz90 causes a G0/G1 arrest in AR-null cells, whereas Jazz167 leads to a G0/G1 arrest in DU145 cells. However, apoptosis only occurred at a maximum of 7% of the total cell population following compound treatments in PC3 and DU145 cells. There was a reduction in cyclin D1 and no significant changes in bcl-2 in DU145 and PC3 cells. Overall, the results showed that Jazz90 and Jazz167 function as cytostatic HDAC inhibitors in AR-null prostate cancer cells.

scholarly journals Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sukhneeraj P. Kaur ◽  
Arti Verma ◽  
Hee. K. Lee ◽  
Lillie M. Barnett ◽  
Payaningal R. Somanath ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cell ◽  
Prostate Cancer Cell ◽  
Bone Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Prostate Cancer Cells

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.

scholarly journals Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristen A. Marcellus ◽  
Tara E. Crawford Parks ◽  
Shekoufeh Almasi ◽  
Bernard J. Jasmin
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Rna Binding ◽  
Prostate Cancer Cell ◽  
Rna Binding Protein ◽  
Migration And Invasion ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Prostate Cells

Abstract Background Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. Methods Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. Results We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. Conclusions Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

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