scholarly journals Early Steps of the Virus Replication Cycle Are Inhibited in Prostate Cancer Cells Resistant to Oncolytic Vesicular Stomatitis Virus

2008 ◽  
Vol 82 (24) ◽  
pp. 12104-12115 ◽  
Author(s):  
Brooke L. Carey ◽  
Maryam Ahmed ◽  
Shelby Puckett ◽  
Douglas S. Lyles
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Vesicular Stomatitis Virus ◽  
Virus Replication ◽  
Oncolytic Virus ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Pc3 Cells ◽  
Vesicular Stomatitis

ABSTRACT Vesicular stomatitis virus (VSV) is currently being studied as a candidate oncolytic virus for tumor therapies due to its potent tumoricidal activity. Previous studies have demonstrated that VSV selectively infects tumor cells due to defects in their antiviral pathways. These defects make them more susceptible to VSV-induced killing than normal cells. However, some cancer cells display differential sensitivity to VSV. Specifically, LNCaP prostate cancer cells are sensitive to infection with VSV, while PC3 prostate cancer cells are relatively resistant to VSV. This suggests that tumor cells vary in the extent to which they develop defects in antiviral pathways and, thus, permit virus replication. The goal of these studies was to identify the step(s) of the viral replication cycle that is inhibited in PC3 cells. Results showed that although attachment of VSV was not significantly different among cell types, penetration was delayed by 10 to 30 min in PC3 cells relative to LNCaP cells. Primary transcription was delayed by 6 to 8 h in PC3 cells relative to LNCaP cells. Similarly, both secondary transcription and viral protein synthesis rates were delayed by about 6 to 8 h. The progressively increasing delay suggests that more than one step is affected in PC3 cells. Analysis of cellular gene expression showed that in contrast to LNCaP cells, PC3 cells constitutively expressed numerous antiviral gene products, which may enhance their resistance to VSV. These data indicate that the use of VSV for oncolytic virus therapy for prostate tumors may require prescreening of tumors for their level of susceptibility.

scholarly journals SIRT1 Modulates the Sensitivity of Prostate Cancer Cells to Vesicular Stomatitis Virus Oncolysis

2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Michela Muscolini ◽  
Luciano Castiello ◽  
Enrico Palermo ◽  
Alessandra Zevini ◽  
Matteo Ferrari ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Cancer Cell ◽  
Vesicular Stomatitis Virus ◽  
Oncolytic Virus ◽  
Prostate Cancer Cells ◽  
Intrinsic Resistance ◽  
Primary Tumors ◽  
Vesicular Stomatitis

ABSTRACT Oncolytic virotherapy represents a promising experimental anticancer strategy, based on the use of genetically modified viruses to selectively infect and kill cancer cells. Vesicular stomatitis virus (VSV) is a prototypic oncolytic virus (OV) that induces cancer cell death through activation of the apoptotic pathway, although intrinsic resistance to oncolysis is found in some cell lines and many primary tumors, as a consequence of residual innate immunity to the virus. In the effort to improve OV therapeutic efficacy, we previously demonstrated that different agents, including histone deacetylase inhibitors (HDIs), functioned as reversible chemical switches to dampen the innate antiviral response and improve the susceptibility of resistant cancer cells to VSV infection. In the present study, we demonstrated that the NAD+-dependent histone deacetylase SIRT1 (silent mating type information regulation 2 homolog 1) plays a key role in the permissivity of prostate cancer PC-3 cells to VSVΔM51 replication and oncolysis. HDI-mediated enhancement of VSVΔM51 infection and cancer cell killing directly correlated with a decrease of SIRT1 expression. Furthermore, pharmacological inhibition as well as silencing of SIRT1 by small interfering RNA (siRNA) was sufficient to sensitize PC-3 cells to VSVΔM51 infection, resulting in augmentation of virus replication and spread. Mechanistically, HDIs such as suberoylanilide hydroxamic acid (SAHA; Vorinostat) and resminostat upregulated the microRNA miR-34a that regulated the level of SIRT1. Taken together, our findings identify SIRT1 as a viral restriction factor that limits VSVΔM51 infection and oncolysis in prostate cancer cells. IMPORTANCE The use of nonpathogenic viruses to target and kill cancer cells is a promising strategy in cancer therapy. However, many types of human cancer are resistant to the oncolytic (cancer-killing) effects of virotherapy. In this study, we identify a host cellular protein, SIRT1, that contributes to the sensitivity of prostate cancer cells to infection by a prototypical oncolytic virus. Knockout of SIRT1 activity increases the sensitivity of prostate cancer cells to virus-mediated killing. At the molecular level, SIRT1 is controlled by a small microRNA termed miR-34a. Altogether, SIRT1 and/or miR-34a levels may serve as predictors of response to oncolytic-virus therapy.

scholarly journals MAP3K7 and CHD1 Are Novel Mediators of Resistance to Oncolytic Vesicular Stomatitis Virus in Prostate Cancer Cells

2020 ◽  
Vol 17 ◽  
pp. 496-507
Author(s):  
Robert S. Bayne ◽  
Shelby Puckett ◽  
Lindsey Ulkus Rodrigues ◽  
Scott D. Cramer ◽  
Jingyun Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Vesicular Stomatitis Virus ◽  
Prostate Cancer Cells ◽  
Vesicular Stomatitis

scholarly journals The Impact of Ang-(1-9) and Ang-(3-7) on the Biological Properties of Prostate Cancer Cells by Modulation of Inflammatory and Steroidogenesis Pathway Genes

2020 ◽  
Vol 21 (17) ◽  
pp. 6227
Author(s):  
Kamila Domińska ◽  
Karolina Kowalska ◽  
Kinga Anna Urbanek ◽  
Dominika Ewa Habrowska-Górczyńska ◽  
Tomasz Ochędalski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Renin Angiotensin System ◽  
Biological Properties ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
M Cell ◽  
Pc3 Cells ◽  
The Impact

The local renin–angiotensin system (RAS) plays an important role in the pathophysiology of the prostate, including cancer development and progression. The Ang-(1-9) and Ang-(3-7) are the less known active peptides of RAS. This study examines the influence of these two peptide hormones on the metabolic activity, proliferation and migration of prostate cancer cells. Significant changes in MTT dye reduction were observed depending on the type of angiotensin and its concentration as well as time of incubation. Ang-(1-9) did not regulate the 2D cell division of either prostate cancer lines however, it reduced the size of LNCaP colonies formed in soft agar, maybe through down-regulation of the HIF1a gene. Ang-(3-7) increased the number of PC3 cells in the S phase and improved anchorage-independent growth as well as mobility. In this case, a significant increase in MKI67, BIRC5, and CDH-1 gene expression was also observed as well as all members of the NF-kB family. Furthermore, we speculate that this peptide can repress the proliferation of LNCaP cells by NOS3-mediated G2/M cell cycle arrest. No changes in expression of BIRC5 and BCL2/BAX ratio were observed but a decrease mRNA proapoptotic BAD gene was seen. In the both lines, Ang-(3-7) improved ROCK1 gene expression however, increased VEGF and NOS3 mRNA was only seen in the PC3 or LNCaP cells, respectively. Interestingly, it appears that Ang-(1-9) and Ang-(3-7) can modulate the level of steroidogenic enzymes responsible for converting cholesterol to testosterone in both prostate cancer lines. Furthermore, in PC3 cells, Ang-(1-9) upregulated AR expression while Ang-(3-7) upregulated the expression of both estrogen receptor genes. Ang-(1-9) and Ang-(3-7) can impact on biological properties of prostate cancer cells by modulating inflammatory and steroidogenesis pathway genes, among others.

scholarly journals Bcl-xL Is Overexpressed in Hormone-Resistant Prostate Cancer and Promotes Survival of LNCaP Cells via Interaction with Proapoptotic Bak

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4960-4967 ◽  
Author(s):  
Carolina Castilla ◽  
Belén Congregado ◽  
David Chinchón ◽  
Francisco J. Torrubia ◽  
Miguel A. Japón ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Topoisomerase I ◽  
Immunohistochemical Analysis ◽  
Gleason Grade ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Pc3 Cells ◽  
Prostate Carcinomas

Androgen-sensitive prostate cancer cells turn androgen resistant through complex mechanisms that involve dysregulation of apoptosis. We investigated the role of antiapoptotic Bcl-xL in the progression of prostate cancer as well as the interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and -independent prostate cancer cells. Immunohistochemical analysis was used to study the expression of Bcl-xL in a series of 139 prostate carcinomas and its association with Gleason grade and time to hormone resistance. Expression of Bcl-xL was more abundant in prostate carcinomas of higher Gleason grades and significantly associated with the onset of hormone-refractory disease. In vivo interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h, Bcl-xL decreased gradually and Bak increased coincidentally with the progress of apoptosis. These results support a model in which Bcl-xL would exert an inhibitory effect over Bak via heterodimerization. We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer.

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

scholarly journals Tamarix Articulata Exhibits Antiproliferative and Antimetastatic Activity by Modulating PI3K-Akt and TGF-β-Mediated Downstream Signaling in Prostate Cancer Cells

2021 ◽  
Author(s):  
Abdullah M Alnuqaydan ◽  
Abdulmajeed G Almutary ◽  
Abdullah M Alajlan ◽  
Abdullah Al Tamim ◽  
Abdullah Alowaifeer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Dependent Manner ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Dose Dependent ◽  
Timp1 Expression ◽  
E Cadherin

Abstract Anticancer drugs mainly kill tumor cells through the apoptosis mechanism, but they can become ineffective when tumor cells are metastatic. Thus, searching for plant-based extracts/compounds to curtail metastasis is extremely important. This study aims to evaluate the anticancer potential of Tamarix articulata (TA) extract against prostate cancer cells. MTT, Brd U, and trypan blue assays was performed to evaluate the cell viability. TUNEL assay were performed to determine apoptotic cells. Clonogenic, wound healing and Boyden chamber assay were conducted to evaluate the anti-clonogenic, anti-motility, and anti-invasive potential of TA. Zymography and immunoblotting were done to check the activity and expression of metalloproteases and proteins associated with metastasis. Our results demonstrated that TA extract significantly inhibits cell viability, clonogenic property, and displays IC₅₀ values in the 245–289 µg/mL range. TA extract significantly abrogates the motility and invasive property of LnCaP cells in a dose-dependent manner. Mechanistically, TA extract downregulates the expression of PI3K-Akt/TGF-β-SMAD2/3 and MMP-2/-9 with concomitant upregulation of TIMP1 expression in LnCaP cells. Additionally, we observe a dose-dependent downregulation of snail and vimentin with the upregulation of E-cadherin protein expression in LnCaP cells. In conclusions, TA extract exhibits an antiproliferative effect, abrogates cell motility and invasion by downregulating PI3K-Akt/TGF-β-SMAD2/3, MMP-2/9, snail, and vimentin with concomitant upregulation of E-cadherin and TIMP1 expression in prostate cancer cells.

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.

A self-assembled π-conjugated system as an anti-proliferative agent in prostate cancer cells and a probe for intra-cellular imaging

RSC Advances ◽  
2014 ◽  
Vol 4 (89) ◽  
pp. 48433-48437 ◽  
Author(s):  
Krishnamoorthy Lalitha ◽  
Preethi Jenifer ◽  
Y. Siva Prasad ◽  
Kumarasamy Muthusamy ◽  
George John ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Renewable Resource ◽  
Cellular Imaging ◽  
Prostate Cancer Cells ◽  
Conjugated Systems ◽  
Pc3 Cells ◽  
Self Assembled

Herein, self-assembled π-conjugated systems derived from renewable resource are reported as a probe for intra-cellular imaging and an anti-proliferative agent for PC3 cells.

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