scholarly journals G Protein-Coupled Receptors (GPCRs)-Mediated Calcium Signaling in Ovarian Cancer: Focus on GPCRs activated by Neurotransmitters and Inflammation-Associated Molecules

2019 ◽  
Vol 20 (22) ◽  
pp. 5568 ◽  
Author(s):  
Predescu ◽  
Crețoiu ◽  
Crețoiu ◽  
Pavelescu ◽  
Suciu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Chemokine Receptors ◽  
Ovarian Cell Lines ◽  
Different Types ◽  
Protein Receptors ◽  
Essential Contribution ◽  
Molecular Signals ◽  
G Protein Coupled

G-coupled protein receptors (GCPR) involve several signaling pathways, some of them being coupled with intracellular calcium (Ca2+) mobilization. GPCRs were involved in migration, invasion and metastasis of different types of cancers, including ovarian cancer. Many studies have discussed the essential contribution of GPCRs activated by steroid hormones in ovarian cancer. However, ovarian cancer is also associated with altered signals coming from the nervous system, the immune system or the inflammatory environment, in which GPCRs are ‘sensing’ these molecular signals. Many studies have been oriented so far on ovarian cell lines (most of them being of human cell lines), and only few studies based on animal models or clinical studies have been devoted to the expression changes or functional role of GPCRs in ovarian cancer. In this paper, we review the alterations of GPCRs activated by neurotransmitters (muscarinic receptors, serotonin receptors, dopamine receptors, adrenoceptors) or inflammation-associated molecules (bradykinin receptors, histamine receptors, chemokine receptors) in ovarian cancer and we discuss their potential as histological biomarkers.

scholarly journals The role of Resveratrol, Sirtuin1 and RXRα as prognostic markers in ovarian cancer

2021 ◽  
Author(s):  
Fangfang Chen ◽  
Thomas Kolben ◽  
Sarah Meister ◽  
Bastian Czogalla ◽  
Theresa M Kolben ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Prognostic Markers ◽  
Gynecologic Cancer ◽  
Resistance Mechanisms ◽  
Tissue Samples ◽  
Advanced Tumor ◽  
Ovarian Cell Lines ◽  
Tumor Stages

Abstract Objective: Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design: 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell-lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting. Results: A correlation of nuclear Sirt1 and RXRα expression could be detected (p=0.006). Co-expression of nuclear RXRα and cytoplasmic (p=0.026) or nuclear (p=0.041) Sirt1 was associated with significantly increased overall survival in advanced tumor stages. Viability was decreased in all cell-lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p=0.025) and significant increased RXR expression in cisA2780 cells (p=0.012). Conclusion: In order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.

scholarly journals The role of resveratrol, Sirtuin1 and RXRα as prognostic markers in ovarian cancer

2021 ◽  
Author(s):  
Fangfang Chen ◽  
Thomas Kolben ◽  
Sarah Meister ◽  
Bastian Czogalla ◽  
Theresa M. Kolben ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Prognostic Markers ◽  
Gynecologic Cancer ◽  
Resistance Mechanisms ◽  
Retinoid X Receptor ◽  
Tissue Samples ◽  
Improve Treatment ◽  
Ovarian Cell Lines

Abstract Objective Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting Results A correlation of nuclear Sirt1 and RXRα expression could be detected (p = 0.006). Co-expression of nuclear RXRα and cytoplasmic (p = 0.026) or nuclear (p = 0.041) Sirt1 was associated with significantly increased overall survival in advanced tumour stages. Viability was decreased in all cell lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p = 0.025) and significant increased RXR expression in cisA2780 cells (p = 0.012) Conclusion In order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.

scholarly journals Atypical Chemokine Receptors in Cardiovascular Disease

2019 ◽  
Vol 119 (04) ◽  
pp. 534-541 ◽  
Author(s):  
Selin Gencer ◽  
Emiel van der Vorst ◽  
Maria Aslani ◽  
Christian Weber ◽  
Yvonne Döring ◽  
...  
Keyword(s):  
G Protein ◽  
Chemokine Receptors ◽  
Cellular Response ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Signalling Pathways ◽  
Atherosclerosis Development ◽  
G Protein Coupled ◽  
Precise Role

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

scholarly journals Role of the G-Protein-Coupled Receptor Signaling Pathway in Insecticide Resistance

2019 ◽  
Vol 20 (17) ◽  
pp. 4300 ◽  
Author(s):  
Ting Li ◽  
Nannan Liu
Keyword(s):  
Insecticide Resistance ◽  
Cell Line ◽  
Signaling Pathway ◽  
G Protein ◽  
Cell Lines ◽  
Sf9 Cells ◽  
Camp Production ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

The G-protein-coupled receptor (GPCR) regulated intracellular signaling pathway is known to be involved in the development of insecticide resistance in the mosquito, Culex quinquefasciatus. To elucidate the specific role of each effector in the GPCR regulating pathway, we initially expressed a GPCR, G-protein alpha subunit (Gαs), adenylate cyclase (AC), and protein kinase A (PKA) in insect Spodoptera frugiperda (Sf9) cells and investigated their regulation function on cyclic AMP (cAMP) production and PKA activity. GPCR, Gαs, and AC individually expressed Sf9 cells showed higher cAMP production as the expression of each effector increased. All the effector-expressed cell lines showed increased PKA activity however. Moreover, Sf9 cytochrome P450 gene expression and cell tolerance to permethrin were examined. The relative expression of CYP9A32gene in Sf9 cells tested was significantly increased in all effector-expressed cell lines compared to a control cell line; these effector-expressed cell lines also showed significantly higher tolerance to permethrin. Inhibitor treatments on each effector-expressed cell line revealed that Bupivacaine HCl and H89 2HCl robustly inhibited cAMP production and PKA activity, respectively, resulting in decreased tolerance to permethrin in all cell lines. The synergistic functions of Bupivacaine HCl and H89 2HCl with permethrin were further examined in Culex mosquito larvae, providing a valuable new information for mosquito control strategies.

scholarly journals Role of notch pathway and HNF1 in cell death induced by HDACs inhibitors in ovarian cancer cell lines, serous and clear cells

2010 ◽  
Vol 4 (S2) ◽  
Author(s):  
Fernanda Silva ◽  
Jacinta Serpa ◽  
Germana Domingues ◽  
Gabriela Silva ◽  
António Almeida ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Notch Pathway ◽  
Cancer Cell Lines ◽  
Clear Cells ◽  
Ovarian Cancer Cell Lines

The role of the glucocorticoid receptor (GR) in inhibiting chemotherapy-induced apoptosis in high-grade serous ovarian carcinoma (HGS-OvCa).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11101-11101
Author(s):  
Erica Michelle Stringer ◽  
Maxwell N. Skor ◽  
Gini F. Fleming ◽  
Suzanne D. Conzen
Keyword(s):  
Ovarian Cancer ◽  
Glucocorticoid Receptor ◽  
Tumor Cell ◽  
Cell Survival ◽  
Cell Lines ◽  
High Grade ◽  
Induced Apoptosis ◽  
Er Alpha ◽  
Ovca Cell

11101 Background: Ovarian cancer is the leading cause of death from gynecologic malignancies. High-grade serous ovarian cancer (HGS-OvCa) is often initially sensitive to platinum-based therapy, but relapse rates remain high. The TCGA recently found that HGS-OvCas have a gene expression and mutational profile similar to that of triple negative breast cancer (TNBC). Previously, our group demonstrated that dexamethasone treatment decreased chemotherapy-induced tumor cell apoptosis in TNBC and HGS-OvCa cell lines. We have also shown that glucocorticoid receptor (GR) activation induces expression of anti-apoptotic genes SGK1 and MKP1/DUSP1 in both HGS-OvCa and TNBC cell lines and in primary human ovarian and TNBC tumors. Methods: We examined glucocorticoid receptor (GR), estrogen receptor (ER), and progesterone receptor (PR) expression in a panel of HGS-OvCa cell lines by Western analysis and qRT-PCR. We also performed apoptosis assays with and without mifepristone, glucocorticoid and/or chemotherapy treatment using IncuCyte live-cell imaging technology in order to measure the effect of GR modulation of chemotherapy sensitivity. Results: HGS-OvCa cell lines (including CAOV3, HeyA8, SKOV3, Monty-1) all had detectable GR expression; HeyA8, SKOV3, and Monty-1 cell lines expressed very low levels of ER-alpha while all other HGS-OvCa cell lines did not express any detectable ER-alpha. Furthermore, none of the HGS-OvCa cell lines tested expressed PR.Apoptosis assays revealed that GR activation significantly inhibited gemcitabine/carboplatin-induced apoptosis in HGS-OvCa cell lines and that mifepristone could reverse this cell survival effect, presumably through GR antagonism. Conclusions: These results suggest that treatment with mifepristone, a GR antagonist, reverses GR-mediated cell survival signaling in HGS-OvCa and increases chemotherapy-induced tumor cell death. To further investigate the role of GR activity in HGS-OvCa, we are currently performing xenograft experiments with chemotherapy +/- mifepristone treatment.

scholarly journals Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

2003 ◽  
Vol 77 (11) ◽  
pp. 6138-6152 ◽  
Author(s):  
Samantha J. Willey ◽  
Jacqueline D. Reeves ◽  
Richard Hudson ◽  
Koichi Miyake ◽  
Nathalie Dejucq ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Cell Lines ◽  
Chemokine Receptors ◽  
Adult Brain ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT The chemokine receptors CCR5 and CXCR4 are the major coreceptors for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). At least 12 other chemokine receptors or close relatives support infection by particular HIV and SIV strains on CD4+ transformed indicator cell lines in vitro. However, the role of these alternative coreceptors in vivo is presently thought to be insignificant. Infection of cell lines expressing high levels of recombinant CD4 and coreceptors thus does not provide a true indication of coreceptor use in vivo. We therefore tested primary untransformed cell cultures that lack CCR5 and CXCR4, including astrocytes and brain microvascular endothelial cells (BMVECs), for naturally expressed alternative coreceptors functional for HIV and SIV infection. An adenovirus vector (Ad-CD4) was used to express CD4 in CD4− astrocytes and thus confer efficient infection if a functional coreceptor is present. Using a large panel of viruses with well-defined coreceptor usage, we identified a subset of HIV and SIV strains able to infect two astrocyte cultures derived from adult brain tissue. Astrocyte infection was partially inhibited by several chemokines, indicating a role for the chemokine receptor family in the observed infection. BMVECs were weakly positive for CD4 but negative for CCR5 and CXCR4 and were susceptible to infection by the same subset of isolates that infected astrocytes. BMVEC infection was efficiently inhibited by the chemokine vMIP-I, implicating one of its receptors as an alternative coreceptor for HIV and SIV infection. Furthermore, we tested whether the HIV type 1 and type 2 strains identified were able to infect peripheral blood mononuclear cells (PBMCs) via an alternative coreceptor. Several strains replicated in Δ32/Δ32 CCR5 PBMCs with CXCR4 blocked by AMD3100. This AMD3100-resistant replication was also sensitive to vMIP-I inhibition. The nature and potential role of this alternative coreceptor(s) in HIV infection in vivo is discussed.

scholarly journals THE ROLE OF GENES RAD50 AND SMARCA5 IN REGULATION OF SENSITIVITY TO CISPLATIN IN TUMOR CELLS OF OVARIAN, HEAD AND NECK CANCER

2017 ◽  
Vol 22 (1) ◽  
pp. 39-43
Author(s):  
A. V Gaponova ◽  
I. G Serebriiskii ◽  
R. G Kiyamova
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cell Lines ◽  
Cancer Cell ◽  
Neck Cancer ◽  
Cancer Cell Lines ◽  
Focus Formation

Aim of the study. To assess the role of genes RAD50 and SMARCA5 in regulation of sensitivity to cisplatin and other anticancer DNA damaging drugs (5-fluorouracil, olaparib), to assess the role of these genes in the response to the DNA damage in ovarian cancer (OVCAR-8) and head and neck cancer cell lines (SCC61, SCC25). Material and Methods. We used small interfering RNAs (siRNAs) (Qiagen,Germany) to deplete either RAD50 and SMARCA5 or control genes and under basal and DNA damaging drug-treatment conditions, we assessed cell viability with the use of Cell Titer Blue reagent (Promega,USA) with following spectrophotometry. To assess the role of genes in response to DNA damage, analysis of phospho-H2AX focus formation was performed by means of using immunofluorescence microscopy. Results. We demonstrated the role of RAD50 and SMARCA5 in regulation of survival and sensitivity of ovarian cancer (OVCAR-8), head and neck cancer cell lines (SCC61, SCC25) to cisplatin and other DNA damaging drugs (5-fluorouracil, olaparib). Our data suggest the role of SMARCA5 in regulation of baseline histone H2AX protein phosphorylation in the absence of DNA damage. Conclusion. Our findings characterize genes RAD50 and SMARCA5 as promising therapeutic targets and predictive markers for response to cisplatin and other DNA damaging drugs in patients with ovarian cancer and squamous cell carcinoma of head and neck.

scholarly journals MiR-624-5p enhances cell resistance against cisplatin via PDGFRA/Stat3/PI3K axis in ovarian cancer

2020 ◽  
Vol 19 (4) ◽  
pp. 691-698
Author(s):  
Lin I-Ju ◽  
Tian YongJie
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Clinical Stage ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay

Purpose: The purpose of this study was to evaluate the role of miR-624-5p in ovarian cancer.Methods: MiR-624-5p expression in ovarian cancer {OC) cell lines and normal cells (NCs) was evaluated and compared the differential miR-624-5p in OC A2780 cells and cisplatin-resistant OC cell line (A2780/DDP). CCK-8 was used to evaluate changes in cell viability of the A2780 and A2780/DDP cell lines as well as silenced miR-624-5p. Western Blot examined the Stat3 and phosphorylated Pi3k. The binding between PDGFRA and miR-624-5p was predicted on Targetscan and verified through Luciferase Reporter Assay. The role of PDGFRA in A2780/DDP by overexpressing PDGFRA was evaluated by RT-qPCR and CCK-8 assays. RT-qPCR assay also measured miR-624-5p expression responsive to different dosages of cisplatin and CCK8 examined viability levels correspondingly. In addition, the interplay of PDGFRA and miR-624-5p by combined downregulation of both miR-624-5pand PDGFRA were evaluated.Results: OC cells had higher miR-624-5p expression than NCs but lower compared to cisplatinresistant A2780/DDP cells. A2780/DDP cells had higher viability than OC cell line A2780. Stat3 and phosphorylated PI3K were activated in A2780/DDP cells. Silencing miR-624-5p led to lower viability inA2780/DDP cells. miR-624-5p expression dropped as the cisplatin concentration increased, resulting in decreasing viability respectively. Luciferase Reporter assay validated the binding of miR-624-5p and PDGFRA in A2780/DDP cells. Overexpressed PDGFRA induced lower cell viability in A2780/DDP cells. Downregulation of PDGFRA partially restored the lowered viability and inhibited Stat3 as well as phosphorylated Pi3k induced by miR-624-5p inhibitor.Conclusion: MiR-624-5p could add to the cellular resistance to cisplatin in OC in-vitro model, which indicated that it might help unveil the mystery of drug-resistance in clinical stage of ovarian cancer. Keywords: MiR-624-5p, resistance, cisplatin, PDGFRA/Stat3/PI3K, ovarian cancer

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