scholarly journals The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

10.5772/55185 ◽  
2013 ◽  
Author(s):  
Maneet Bhatia ◽  
Therese C. ◽  
Giovanna Di ◽  
Kathryn F.
Keyword(s):  
Cancer Cells ◽  
Signalling Pathways ◽  
Oxygen Environment

scholarly journals Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lee-Chin Chan ◽  
Jeevanathan Kalyanasundram ◽  
Sze-Wei Leong ◽  
Mas Jaffri Masarudin ◽  
Abhi Veerakumarasivam ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Newcastle Disease Virus ◽  
Cancer Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Persistent Infection ◽  
Signalling Pathways ◽  
Bladder Cancer Cells ◽  
Transcriptomic Changes

Abstract Background Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood. Methods In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR. Results Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV. Conclusions This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.

Synergistic Cytotoxicity Effect of 5-fluorouracil and SHP2 Inhibitor Demethylincisterol A3 on Cervical Cancer Cell

2021 ◽  
Vol 21 ◽  
Author(s):  
Yang Liu ◽  
Hua Fu ◽  
Li Zuo
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Signalling Pathways ◽  
Combined Effects ◽  
Cytotoxic Effects ◽  
Promising Strategy ◽  
Synergistic Cytotoxicity ◽  
Cervical Cancer Cells ◽  
Synergistic Cytotoxic Effect

Background: Demethylincisterol A3 (DTA3) has been identified as an SHP2 inhibitor and suppresses the growth of many cancer cells. 5-Fluorouracil (5-FU) is widely used for the clinical treatment of various cancers. However, the combined effects of 5-FU and DTA3 on cervical cancer cells remain unknown. Objective: his study evaluates the mechanism of the combined effects of 5-FU and DTA3 in cervical cancer cells. Methods: The synergistic cytotoxic effects of 5-FU and DTA3 in cervical cancer cells were calculated. Apoptosis was analysed by flow cytometry. Western blot analyses were used to examine the related signalling pathways. Results: DTA3 and 5-FU synergized to induce apoptosis and repress proliferation of cervical cancer cells by downregulating the activation of PI3K/AKT and NF-κB signalling pathway. We provided evidence that the upregulation of SHP2 expression by transfection significantly inhibited the cytotoxicity of 5-FU and DTA3. SHP2 knockdown enhanced the antiproliferation activity of 5-FU, indicating targeting SHP2 sensitized cervical cancer cells to 5-FU. Conclusion: Our study demonstrates that SHP2 inhibitor DTA3 and 5-FU have a synergistic cytotoxic effect on cervical cancer cells. The synergistic combination of SHP2 inhibitor and 5-FU may present a promising strategy for the treatment of cervical cancer.

Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 522-522 ◽  
Author(s):  
Markus Hermann Moehler ◽  
Annett Mueller ◽  
Erika Bachmann ◽  
Carl Christoph Schimanski ◽  
Peter Robert Galle
Keyword(s):  
Gastric Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Gastrointestinal Cancer ◽  
Human Colon ◽  
Signalling Pathways ◽  
Wild Type ◽  
Pi3k Inhibitors ◽  
Apoptotic Effects

522 Background: New targeted agents against tyrosine kinases expand the standard therapy in oncology. However, tumor resistance is still a challenge, particularly induced by mutations in growth-related signalling cascades. 20% and 10% of patients with human colon and gastric cancer carry PI3K mutations and do not react to receptor blocking therapies. Recently, selective tyrosine kinase inhibitors have been generated which block PI3K signalling pathways in tumor cells. Their therapeutically role has not yet been clarified. Methods: To define inhibitory and pro-apoptotic effects of the 2 PI3K inhibitors BEZ235 and BKM120 3 human colon cancer (HT-29, HCT-116, DLD-1) and 3 gastric cancer cell lines (NCI-n87, AGS, MKN-45) with different PIK3CA mutation status were used. First, viability, apoptosis and caspase assays were performed during incubation with inhibitors alone or combined with cytotoxic agents. Second, molecular consequences for cell cycle and the signalling pathways were analysed by defining the protein levels by FACS and Western blot. Results: Both PI3K inhibitors BEZ235 and BKM120 induced concentration dependently a significant reduction in viability and an increase in apoptotic death, while mutated cells reacted more sensitive to treatment. BKM120 had a higher efficiency than the dual PI3K/mTOR inhibitor BEZ235. BEZ235 alone caused a G1 arrest in tumor cells. In contrast, BKM120 induced a G2 shift in all gastrointestinal cancer cells. There was a clear downregulation in AKT signalling, and for BEZ235 an additional inhibition of mTOR pathway. Furthermore, BEZ235 caused synergistic induction of apoptosis combined with irinotecan in colon cancer. Combinations with 5-fluoruracil and the 2 substances induced additive apoptotic effects. Human gastric cancer cells were less sensitive to BEZ235 and BKM120. Conclusions: In general, we found higher pro-apoptotic effects for all cell lines and in special cases a better response of resistant mutant cells. Our data support the clinical development of these PI3K inhibitors BEZ235 and BKM120 as potential targeting agents for patients with different wild-type or mutated gastrointestinal cancer cells.

scholarly journals Co-Activation of TGFβ and Wnt Signalling Pathways Abrogates EMT in Ovarian Cancer Cells

2017 ◽  
Vol 41 (4) ◽  
pp. 1336-1345 ◽  
Author(s):  
Tulika Mitra ◽  
Sib Sankar Roy
Keyword(s):  
Ovarian Cancer ◽  
Growth Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signalling ◽  
Luciferase Assay ◽  
Signalling Pathways ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Co Activation

Background/Aims: The aggressive property of ovarian cancer (OC) in terms of epithelial-mesenchymal transition (EMT), proliferation and metastasis are of major concern. Different growth factors including TGFβ are associated with regulating these molecular events but the underlying mechanisms remain unclear. The aim of this report is to decipher the regulation of EMT by co-activation of TGFβ and Wnt signalling cascades in gaining malignancy. Methods: The expression of the different components of signalling events were analyzed by QPCR, Western blot, Immunofluorescence microscopy and flow cytometry. β-catenin promoter activity was checked by luciferase assay. Results: We observed reduced EMT in ovarian cancer cells upon co-activation with TGFβ1 and LiCl as shown by the expressions of epithelial/mesenchymal markers and the EMT promoting factor, Snail1, accompanied by decrease in the invasion and migration of the cells compared to individual pathway activation. A detailed study of the mechanism suggested reduction in the β-catenin and p-GSK3b (Ser 9) levels to be the driving cause of this phenomenon, which was reversed upon co-activation with higher concentrations of LiCl. Conclusions: Therefore, tumourigenesis might be affected by the concentration of ligand/ growth factors for the respective signalling pathways activated in the tumour microenvironment and interaction between them might alter tumourigenesis.

scholarly journals Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells

Open Biology ◽  
2016 ◽  
Vol 6 (12) ◽  
pp. 150262 ◽  
Author(s):  
Chin-Yo Lin ◽  
Erica L. Kleinbrink ◽  
Fabien Dachet ◽  
Juan Cai ◽  
Donghong Ju ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Signalling Pathways ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.

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