scholarly journals Effects of the Bone/Bone Marrow Microenvironments on Prostate Cancer Cells and CD59 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bo Yan ◽  
Yan Li ◽  
Shaoju Min ◽  
Peng Zhang ◽  
Bin Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Bone Marrow ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
Prostate Cancer Cells ◽  
Pc3 Cells ◽  
Bone Marrow Microenvironments

Objective. To evaluate the effects of human bone marrow mesenchymal stem cells (hBMSCs) and osteoblasts (hFOB1.19) on PC3 prostate cancer cells. Methods. To simulate the in vivo interaction between the bone/bone marrow microenvironments and prostate cancer cells, we established cocultures of PC3 cells with hBMSC or hFOB1.19 cells and evaluated their effects on the proliferation, cell cycle distribution, cell migration, and invasion of PC3 cells. Quantitative reverse transcription polymerase chain reaction was used to detect CD59 mRNA expression in PC3 cells. The expression of receptor activator of nuclear factor- (NF-) κB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), CD59, NF-κB (p50 subunit), and cyclin D1 in PC3 cells was analyzed by immunofluorescence and western blotting. Results. hBMSCs and hFOB1.19 cells enhanced the proliferation, migration, and invasion of PC3 cells; increased the proportion of PC3 cells in the S and G2/M phases of the cell cycle; and upregulated RANK, RANKL, OPG, CD59, cyclin D1, and NF-κB (p50 subunit) expression by PC3 cells. The RANKL inhibitor, scutellarin, inhibited these effects in PC3-hFOB1.19 cocultures. Conclusion. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.

scholarly journals TGF-β Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1768-1779 ◽  
Author(s):  
BaoHan T. Vo ◽  
Derrick Morton ◽  
Shravan Komaragiri ◽  
Ana C. Millena ◽  
Chelesie Leath ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Protein Levels ◽  
Prostate Cells ◽  
Pc3 Cells ◽  
Cox 2

Abstract TGF-β plays an important role in the progression of prostate cancer. It exhibits both tumor suppressor and tumor-promoting activities. Correlations between cyclooxygenase (COX)-2 overexpression and enhanced production of prostaglandin (PG)E2 have been implicated in cancer progression; however, there are no studies indicating that TGF-β effects in prostate cancer cells involve PGE2 synthesis. In this study, we investigated TGF-β regulation of COX-1 and COX-2 expression in prostate cancer cells and whether the effects of TGF-β on cell proliferation and migration are mediated by PGE2. COX-1 protein was ubiquitously expressed in prostate cells; however, COX-2 protein levels were detected only in prostate cancer cells. TGF-β treatment increased COX-2 protein levels and PGE2 secretion in PC3 cells. Exogenous PGE2 and PGF2α had no effects on cell proliferation in LNCaP, DU145, and PC3 cells whereas PGE2 and TGF-β induced migration and invasive behavior in PC3 cells. Only EP2 and EP4 receptors were detected at mRNA levels in prostate cells. The EP4-targeting small interfering RNA inhibited PGE2 and TGF-β-induced migration of PC3 cells. TGF-β and PGE2 induce activation of PI3K/AKT/mammalian target of rapamycin pathway as indicated by increased AKT, p70S6K, and S6 phosphorylation. Rapamycin completely blocked the effects of TGF-β and PGE2 on phosphorylation of p70S6K and S6 but not on AKT phosphorylation. PGE2 and TGF-β induced phosphorylation of AKT, which was blocked by antagonists of PGE2 (EP4) receptors (L161982, AH23848) and PI3K inhibitor (LY294002) in PC3 cells. Pretreatment with L161982 or AH23848 blocked the stimulatory effects of PGE2 and TGF-β on cell migration, whereas LY294002 or rapamycin completely eliminated PGE2, TGF-β, and epidermal growth factor-induced migration in PC3 cells. We conclude that TGF-β increases COX-2 levels and PGE2 secretion in prostate cancer cells which, in turn, mediate TGF-β effects on cell migration and invasion through the activation of PI3K/AKT/mammalian target of rapamycin pathway.

scholarly journals Formononetin Promotes Cell Cycle Arrest via Downregulation of Akt/Cyclin D1/CDK4 in Human Prostate Cancer Cells

2014 ◽  
Vol 34 (4) ◽  
pp. 1351-1358 ◽  
Author(s):  
Tianyu Li ◽  
Xinge Zhao ◽  
Zengnan Mo ◽  
Weihua Huang ◽  
Haibiao Yan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Cycle Arrest

scholarly journals Inhibitory role of circRNA_100395 in the proliferation and metastasis of prostate cancer cells

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199221
Author(s):  
Haitian He ◽  
Jianhua Li ◽  
Mayao Luo ◽  
Qiang Wei
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Counting ◽  
Cell Cycle Distribution ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Endogenous Expression ◽  
Proliferation And Metastasis

Objective Circular RNAs (circRNAs) are non-coding RNAs with high cancer-specific expression and the potential for regulating tumorigenesis. CircRNA_100395 is expressed at low levels in many cancers and is involved in the regulation of tumor cell proliferation and metastasis. However, its expression and function in prostate cancer remain unclear. Methods Endogenous expression levels of circRNA_100395 and microRNA-1228 (miR-1228) in prostate cancer tissue samples and cell lines were detected by quantitative reverse transcription-polymerase chain reaction. Cell proliferation, invasion, and migration, cell cycle distribution, and epithelial–mesenchymal transition (EMT) were analyzed in circRNA_100395-overexpressing prostate cancer cells by Cell Counting Kit-8, flow cytometry, Transwell assay, and western blotting, respectively. Results CircRNA_100395 expression was downregulated in cancerous prostate tissues relative to adjacent normal tissues. CircRNA_100395 expression was negatively correlated with tumor size, Gleason score, tumor stage, and lymph node metastasis. Moreover, circRNA_100395 overexpression inhibited cell proliferation, altered cell cycle distribution, reduced cell migration and invasion abilities, and suppressed EMT in prostate cancer cells. Moreover, miR-1228 was a direct downstream target of circRNA_100395, and the anti-tumor ability of circRNA_100395 was significantly reversed by miR-1228. Conclusion This study identified circRNA_100395 as an anti-tumor circRNA and a potential therapeutic target for prostate cancer.

Cleaved High Molecular Weight Kininogen (HKa) and Kininostatin (D5) Induce Apoptosis and Inhibit Migration and Invasion of Human Prostate Cancer Cells by Preventing AKT Phosphorylation and Cyclin D1 Synthesis and Disrupting the Interaction of UPAR and EGFR.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 405-405
Author(s):  
Yuchuan Liu ◽  
Robin Pixley ◽  
Mario Fusaro ◽  
Robert W. Colman
Keyword(s):  
Prostate Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Human Prostate ◽  
Migration And Invasion ◽  
Plasma Kallikrein ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Du145 Cells

Abstract Tumor metastasis is a major factor in the mortality rate in human prostate cancer. Upregulation and activation of EGFR and/or uPAR in a variety of cancers have been shown to be associated with poor prognosis. HK, a component of the plasma kallikrein-kinin system, can be hydrolyzed by plasma kallikrein to bradykinin and HKa. HKa and D5 both have been demonstrated to have potent anti-angiogenic activity in vitro and in vivo. We previously published that D5 directly inhibits human colon carcinoma cell (HCT-116) proliferation in vitro by blocking the G1/S transition in the cell cycle. We now show that HKa [100 nM] inhibits the migration of human prostate tumor cell (DU145) about 50%. Cyclin D1 can activate p21 and p27 with concomitant cell migration. DU145 cells rapidly increase cyclin D1 synthesis in response to bFGF [1.2 nM]. HKa suppresses cyclin D1 expression as shown by Western blotting as well as cell immunoflourescence. Stimulation by bFGF or VEGF results in clustering of uPAR and EGFR on the surface of DU145 cells. Immunoflourescence shows that the addition of HKa disrupts the co-localization of uPAR and EGFR. HKa or a monoclonal antibody against uPAR decreases the phosphorylation of EGFR at Tyr 1173. The phosphorylation of ERK and AKT, which are downstream effectors of EGFR, is also inhibited by HKa. Kininostatin [300nM] induced apoptosis of human prostate cancer cells challenged with uPA [50 nM] or EGF [6.7 nM]. Matrigel invasion assay reveals that HKa [100 nM] decreases the invading cell number by 90%. These novel data indicate that HKa and kininostatin induce apoptosis and inhibit migration and invasion of human prostate cancer cells, indicating the therapeutic potential of kininostatin in metastasis human prostate cancer.

Eupatilin Inhibits the Proliferation and Migration of Prostate Cancer Cells through Modulation of PTEN and NF-κB Signaling

2020 ◽  
Vol 20 ◽  
Author(s):  
Riza Serttas ◽  
Cagla Koroglu ◽  
Suat Erdogan
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Background: Despite advances in treatment of prostate cancer, side effects and the risks of developing drug resistance require new therapeutic agents. Eupatilin is a secondary metabolite of Artemisia asiatica and has shown potential anti-tumor activity in some cancers, but its potential in prostate cancer treatment has not yet been evaluated. Objective: The aim of the study was to investigate the effectiveness of eupatilin on prostate cancer cell proliferation and migration. Methods: Human prostate cancer PC3 and LNCaP cells were exposed to eupatilin and its efficacy on cell survival was determined by MTT test. Apoptosis and cell cycle phases were evaluated by image-based cytometer. Cell migration and invasion was evaluated by wound healing and matrigel migration assays; the expression of mRNA and protein were assessed by RT-qPCR and Western blot,respectively. Results: Eupatilin time- and dose-dependently reduced the viability of prostate cancer cells. Exposure of PC3 cells to 12.5 µM - 50 µM eupatilin resulted in apoptosis by upregulating the expression of caspase 3, Bax and cytochrome c. Annexin V assessment also confirmed that eupatilin causes apoptosis. The treatment significantly upregulated mRNA expression of p53, p21, and p27, causing cell cycle arrest in the G1 phase. Administration of eupatilin inhibited migration and invasion of the cells by down-regulating the expression of Twist, Slug and MMP-2, -7. In addition, the agent increased protein expression of tumor suppressor PTEN, while transcription factor NF-κB expression was reduced. Conclusion: Eupatilin strongly prevents proliferation of prostate cancer cells, and suppresses migration and invasion. Because of its therapeutic potential, the clinical use of eupatilin in prostate cancer should also be supported by in vivo studies.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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.

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