scholarly journals Amphiregulin-EGFR Autocrine Signaling Mediates Neutrophil Elastase-Triggered Prostate Cancer Progression

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1010-A1011
Author(s):  
Zhiguang Xiao ◽  
Stephen R Hammes
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Neutrophil Elastase ◽  
Dependent Manner ◽  
Prostate Cell ◽  
Erk Activation ◽  
Prostate Cells ◽  
Erk Phosphorylation

Abstract Neutrophil elastase (NE) is a serine protease stored in neutrophil azurophilic granules. Growing evidence indicates that NE is intimately involved in the activities of proinflammatory cytokines / chemokines, growth factors, and cell surface receptors. These molecular regulations can modulate innate immune responses as well as directly promote cancer cell outgrowth. To date, however, little is known regarding the molecular mechanisms underlying the stimulatory properties of NE in cancer cells. Here we examine NE effects on prostate cells, demonstrating that NE triggers proliferative signals and cell migration in six prostate cell lines representing the spectrum of prostate cell malignancy, including normal prostatic epithelium, benign prostatic hypertrophy, and metastatic prostate cancer. Using ERK activation as a read-out, we show that NE promotes ERK phosphorylation in a dose dependent manner, and time course study further reveal a sustained ERK activation upon NE treatment. Western blot evaluation demonstrates strong EGFR expression in cell lines derived from normal and benign prostatic gland, and preferential expression in hormone resistant versus hormone responsive cells. In agreement with EGFR-dependent mitogenic signaling, activation of ERK is abrogated by siRNA-mediated EGFR knockdown, as well as by pretreatment of cells with irreversible EGFR inhibitor AG1478. Importantly, NE evokes cancer cell migration at a lower range of NE concentrations relative to nonneoplastic cells. In prostate cells, from a total of seven EGFR ligands, amphiregulin (AREG) is predominantly expressed, and the addition of NE results in the release of AREG. Moreover, AREG gene silencing by siRNA or inhibition of AREG biological activity by neutralizing antibody, prevents NE-induced ERK phosphorylation and cell migration. Together, our study reveals a distinct and essential role of AREG-EGFR signaling axis in NE-triggered prostatic cellular response.

scholarly journals Some Wild Edible Mushroom Anticancer Activity Against Prostate Cell Lines

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 40
Author(s):  
Hatice Bekci ◽  
Mustafa Cam ◽  
Ahmet Cumaoglu
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Prostate Cancer Cell Lines ◽  
Prostate Cell

Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic products, dietary supplements and functional food production. The purpose of the research was to evaluate these derivatives against in vitro to obtain novel specific and effective anticancer agents against prostate cancer. In the study, Amanita caesarea, Sparassis crispa, Lepista nuda, Auricularia auricula, Tricholoma terreum and Lentinus tigrinus fungi were used. Anticancer activities of the compounds were evaluated in vitro by using MTT method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. The most effective among these fungus species biological activity against PC3 cancer cell line (IC50 = 327.34 µM), against DU-145 (IC50 = 459.19 µM).

scholarly journals Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines

2021 ◽  
Vol 14 (7) ◽  
pp. 670
Author(s):  
Mariana Brütt Pacheco ◽  
Vânia Camilo ◽  
Nair Lopes ◽  
Filipa Moreira-Silva ◽  
Margareta P. Correia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Histone Deacetylase Inhibitors ◽  
Combined Treatment ◽  
Dependent Manner ◽  
Prostate Cell ◽  
Methylation Inhibitor ◽  
Clonogenic Potential ◽  
Important Player ◽  
Novel Therapeutic Strategies

Among the well-established alterations contributing to prostate cancer (PCa) pathogenesis, epigenetics is an important player in its development and aggressive disease state. Moreover, since no curative therapies are available for advanced stage disease, there is an urgent need for novel therapeutic strategies targeting this subset of patients. Thus, we aimed to evaluate the combined antineoplastic effects of DNA methylation inhibitor hydralazine and histone deacetylase inhibitors panobinostat and valproic acid in several prostate cell lines. The effect of these drugs was assessed in four PCa (LNCaP, 22Rv1, DU145 and PC-3) cell lines, as well as in non-malignant epithelial (RWPE-1) and stromal (WPMY-1) cell lines, using several assays to evaluate cell viability, apoptosis, proliferation, DNA damage and clonogenic potential. We found that exposure to each epidrug separately reduced viability of all PCa cells in a dose-dependent manner and that combined treatments led to synergic growth inhibitory effects, impacting also on colony formation, invasion, apoptotic and proliferation rates. Interestingly, antitumoral effects of combined treatment were particularly expressive in DU145 cells. We concluded that hydralazine and panobinostat attenuate malignant properties of PCa cells, constituting a potential therapeutic tool to counteract PCa progression.

Cerebellar Degeneration-Related Autoantigen 1 (CDR1) Gene Expression in Prostate Cancer Cell Lines

2014 ◽  
Vol 29 (3) ◽  
pp. 288-290 ◽  
Author(s):  
Michele Salemi ◽  
Filippo Fraggetta ◽  
Antonio Galia ◽  
Pietro Pepe ◽  
Laura Cimino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cerebellar Degeneration ◽  
Normal Prostate ◽  
Prostate Cell ◽  
Prostate Cell Line ◽  
Normal Prostate Cell

Prostate cancer (PCa) is the most frequent cancer among men in many developing countries, and the second leading cause of cancer-related death in men. A genetic component has been implicated in PCa onset and development. The cerebellar degeneration-related autoantigen 1 ( CDR1) gene, mapping in Xq26-q27.2, is expressed in cerebrum, cerebellum, heart, lung, liver, and kidney. In addition, CDR1 expression has been detected in neuroblastoma, renal carcinoma cell lines, and other cancer cell lines. In this study, we investigated the expression of the CDR1 gene in the LNCaP and PC-3 PCa cell lines, and in the PNT1A normal prostate cell line. CDR1 mRNA expression was evaluated by qRT-PCR. We found that the CDR1 gene was overexpressed in the LNCaP and PC-3 PCa cell lines as compared with the PNT1A normal prostate cell line. These data suggest that CDR1 could be a new biomarker for PCa identification.

scholarly journals The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4716-4726 ◽  
Author(s):  
Sumudra Periyasamy ◽  
Manya Warrier ◽  
Manoranjani P. M. Tillekeratne ◽  
Weinian Shou ◽  
Edwin R. Sanchez
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Cyclosporin A ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Lncap Cells ◽  
Androgen Ablation ◽  
Prostate Cells

The androgen receptor (AR) contributes to growth of prostate cancer even under conditions of androgen ablation. Thus, new strategies to target AR activity are needed. The AR interacts with the immunophilin FK506-binding protein 52 (FKBP52), and studies in the FKBP52 knockout mouse have shown that this protein is essential to AR activity in the prostate. Therefore, we tested whether the immunophilin ligand FK506 affected AR activity in prostate cancer cell lines. We also tested the hypothesis that the AR interacts with another immunophilin, cyclophilin 40 (Cyp40), and is regulated by its cognate ligand cyclosporin A (CsA). We show that levels of FKBP52, FKBP51, Cyp40, and a related co-chaperone PP5 were much higher in prostate cancer cells lines [(LNCaP), PC-3, and DU145] compared with primary prostate cells, and that the AR of LNCaP cells can interact with Cyp40. In the absence of androgen, CsA caused inhibition of cell growth in the AR-positive LNCaP and AR-negative PC-3 and DU145 cell lines. Interestingly, FK506 only inhibited LNCaP cells, suggesting a dependence on the AR for this effect. Both CsA and FK506 inhibited growth without inducing apoptosis. In LNCaP cells, CsA completely blocked androgen-stimulated growth, whereas FK506 was partially effective. Further studies in LNCaP cells revealed that CsA and FK506 were able to block or attenuate several stages of AR signaling, including hormone binding, nuclear translocation, and activity at several AR-responsive reporter and endogenous genes. These findings provide the first evidence that CsA and FK506 can negatively modulate proliferation of prostate cells in vitro. Immunophilins may now serve as new targets to disrupt AR-mediated prostate cancer growth.

scholarly journals Effect of 1-Carbaldehyde-3,4-dimethoxyxanthone on Prostate and HPV-18 Positive Cervical Cancer Cell Lines and on Human THP-1 Macrophages

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3721
Author(s):  
Rui Medeiros ◽  
Bruno Horta ◽  
Joana Freitas-Silva ◽  
Jani Silva ◽  
Francisca Dias ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Metabolic Activity ◽  
Cancer Cell Lines ◽  
No Production ◽  
Prostate Cell ◽  
Raw264.7 Macrophages

Xanthone derivatives have shown promising antitumor properties, and 1-carbaldehyde-3,4-dimethoxyxanthone (1) has recently emerged as a potent tumor cell growth inhibitor. In this study, its effect was evaluated (MTT viability assay) against a new panel of cancer cells, namely cervical cancer (HeLa), androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer, and nonsolid tumor derived cancer (Jurkat) cell lines. The effect of xanthone 1 on macrophage functions was also evaluated. The effect of xanthone 1-conditioned THP-1 human macrophage supernatants on the metabolic viability of cervical and prostate cancer cell lines was determined along with its interference with cytokine expression characteristic of M1 profile (IL-1 ≤ β; TNF-α) or M2 profile (IL-10; TGF-β) (PCR and ELISA). Nitric oxide (NO) production by murine RAW264.7 macrophages was quantified by Griess reaction. Xanthone 1 (20 μM) strongly inhibited the metabolic activity of the cell lines and was significantly more active against prostate cell lines compared to HeLa (p < 0.05). Jurkat was the cell most sensitive to the effect of xanthone 1. Compound 1-conditioned IL-4-stimulated THP-1 macrophage supernatants significantly (p < 0.05) inhibited the metabolic activity of HeLa, LNCaP, and PC-3. Xanthone 1 did not significantly affect the expression of cytokines by THP-1 macrophages. The inhibiting effect of compound 1 observed on the production of NO by RAW 264.7 macrophages was moderate. In conclusion, 1-carbaldehyde-3,4-dimethoxyxanthone (1) decreases the metabolic activity of cancer cells and seems to be able to modulate macrophage functions.

Screening of SirT1 activating compounds and their cytotoxicity in prostate cancer cell lines.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13545-e13545
Author(s):  
Maofu Fu ◽  
Nagarajan Pattabiraman ◽  
Chenguang Wang ◽  
Xiaoming Ju ◽  
Anthony Sauve ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Small Molecules ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Epithelial Cell Line ◽  
Prostate Cancer Cell Lines ◽  
Prostate Cell

e13545 Background: Our previous studies demonstrated that the human androgen receptor (AR) is an acetylated protein, and acetylation of the AR in the hinge region is essential for its ligand-dependent transactivation. The AR acetylation mimic mutant, ARK630Q, and a somatic mutation from the prostate cancer patient at the AR acetylating motif, ARK630T, showed enhanced receptor/coactivator binding and led to accelerated prostate cancer cell growth. SirT1, an NAD+-dependent class III HDAC, suppresses AR and inhibits prostate cell proliferation via deacetylation of AR. Deletion of the SirT1 gene in mice resulted in prostatic intraepithelial neoplasia (PIN) lesion formation associated with reduced autophagy. Our hypothesis is that small molecules with SirT1 activating properties could be potential novel agents for treatment of AR-expressing prostate cancer. Methods: We performed in-silico screening for small molecule antagonists of SirT1 based on computational model prediction of a known SirT1 activator, resveratrol, and identified potential activators for SirT1. The cytotoxicity of these compounds to the prostate cancer cell lines was tested by MTT assay. Results: Among the twelve compounds tested, three compounds, C5, C6 and C10, were found to inhibit AR expression in LNCaP cells and have cytotoxicity in several prostate cell lines including LNCaP, C4W2 and NeuT-transformed prostate epithelial cell line at concentration of 50 µM. Conclusions: Currently, we are testing the effects of these small molecules on the NAD+-dependent deacetylation activity of SirT1 and their effects on AR acetylation as its molecular mechanism of cell growth inhibition. The ultimate goal of this study is to develop early phase clinical trials in prostate cancer patients by blocking AR acetylation using these SirT1 activators.

scholarly journals Identification and characterization of a prostate-specific androgen-independent protein-binding site in the probasin promoter

2003 ◽  
Vol 371 (3) ◽  
pp. 843-855 ◽  
Author(s):  
Lillian H. Y. YEUNG ◽  
Jason T. READ ◽  
Pernille SORENSON ◽  
Colleen C. NELSON ◽  
Martin GLEAVE ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Site Directed Mutagenesis ◽  
Independent Manner ◽  
Strong Basis ◽  
Prostate Cell ◽  
Nuclear Extracts ◽  
Androgen Independent

In this study we investigated the combination of transcription factors and proteins binding to the proximal part of the prostate-specific probasin (PB) promoter. Using DNaseI in vitro footprinting, several protected regions were identified on the proximal PB promoter (nucleotides −286 to +28 relative to the transcription start site) when nuclear extracts from LNCaP, a human prostate cancer cell line, were used. Four of the protected areas were observed only when LNCaP nuclear extracts treated with synthetic androgen (10 nM R1881) were used. Two other regions, referred to as FPI and FPII, showed protection regardless of the presence or absence of androgen. When DNaseI footprinting was done using other prostate and non-prostate nuclear extracts, protection of the FPII region was only seen in prostate cell lines. These androgen-independent regions were further tested for tissue and binding specificity using the electrophoretic mobility-shift assay. Eight complexes formed with the FPI probe while four complexes were observed with the FPII probe on incubation with the tested nuclear extracts. Methylation protection assays reveal that prostate cancer cell lines yield slightly different protection patterns for some of the protein complexes formed with non-prostate-derived cell lines, suggesting the presence of prostate-enriched or -exclusive proteins. Site-directed mutagenesis of the protected nucleotides within FPII resulted in a significant reduction in expression from the PB promoter. Identification of proteins binding to the FPII region revealed the participation of nuclear factor I (NF-I) or a closely related protein, although other unknown proteins are also involved. Defining the DNA and protein components that dictate prostate-specific expression of the PB promoter in an androgen-independent manner would provide a strong basis for the design and development of a gene therapy for systemic treatment of androgen-independent prostate cancer.

scholarly journals Autophagy Mediates Leptin-Induced Migration and ERK Activation in Breast Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Alin García-Miranda ◽  
Karen Aylín Solano-Alcalá ◽  
José Benito Montes-Alvarado ◽  
Arely Rosas-Cruz ◽  
Julio Reyes-Leyva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Morphological Changes ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Erk Activation ◽  
Erk Phosphorylation

Autophagy is an intracellular recycling process active in eukaryotic cells that involves the formation of an autophagosome which delivers cytoplasmic components to the lysosome for degradation. This process occurs at low rates under basal conditions, but it can be induced by diverse types of stress such as starvation, hypoxia, metabolic disorders or in response to hormones, including leptin. Leptin is considered a pro-tumorigenic protein whose circulating levels have been related to bad prognosis in obese breast cancer patients. It has been recently demonstrated that leptin can induce autophagy in cancer cell lines from different tissues, suggesting that autophagy could modulate the pro-tumorigenic effects associated with leptin. In this study, the role of autophagy in leptin-induced proliferation, migration, apoptosis and ERK phosphorylation in breast cancer cell lines was evaluated. Although leptin differentially induced autophagy in the breast cancer cell lines tested, autophagy inhibition reduced leptin-induced cell proliferation in MCF7 cells and decreased cell migration, ERK activation, and impaired morphological changes in both cell lines. Our data demonstrates an important role for basal autophagy or leptin-induced autophagy in leptin-induced migration and ERK phosphorylation in breast cancer cell lines, suggesting a potential use for the inhibition of autophagy in breast cancer associated with obesity.

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