M2013 Effect of Targeting the Neurokinin-1 Receptor On the Transition of Chronic Inflammation to Dysplasia

Pagan, Beatriz; Isidro, Angel A.; Coppola, Domenico; Wu, Jie; Appleyard, Caroline B.

doi:10.1016/s0016-5085(09)62147-8

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These two domains are separated by a cleft, which has been found to bind ATP, ATP analogues, and ATP inhibitors in previous studies (Stamos et al, 2002). Previous experimental studies of colitis showed that EGFR may regulate inflammatory cytokine production (Lu et al, 2014;El Mahdy et al, 2023), and that the EGFR inhibitor, erlotinib, protects from chronic inflammation and development of dysplasia (Pagán et al, 2011). However, some studies show that EGFR activation may also protect from colitis-associated cancer (Dubé et al, 2012;Dubé et al, 2018).…”

Section: Discussionmentioning

confidence: 95%

Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies

Mohamed,

El-Shafae,

Fikry

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Ulcerative colitis (UC) is an inflammatory bowel disease that is often resistant to current treatment options, leading to a need for alternative therapies. Herbal products have shown promise in managing various conditions, including UC. However, the potential of Casuarina glauca branchlets ethanolic extract (CGBRE) in treating UC has not been explored. This study aimed to analyze the chemical composition of CGBRE and evaluate its efficacy in UC treatment through in silico and in vivo experiments. LC-ESI-MS/MS was used to identify 86 compounds in CGBRE, with 21 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 171 potential UC targets for the bioactive compounds, including EGFR, LRRK2, and HSP90 as top targets, which were found to bind to key CGBRE compounds through molecular docking. Molecular docking findings suggested that CGBRE may be effective in the prevention or treatment of ulcerative colitis mediated by these proteins, where key CGBRE compounds exhibited good binding affinities through formation of numerous interactions. In vivo studies in rats with acetic acid-induced UC demonstrated that oral administration of 300 mg/kg CGBRE for 6 days reduced UC symptoms and colonic expression of EGFR, LRRK2, and HSP90. These findings supported the therapeutic potential of CGBRE in UC and suggested the need for further preclinical and clinical investigation.

show abstract

Section: Discussionmentioning

confidence: 95%

Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies

Mohamed,

El-Shafae,

Fikry

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…[12] Erlotinib is a quinazoline derivative drug and tyrosine kinase inhibitor, which acts on the EGFR to inhibit the signal transduction pathway implicated in cell proliferation, thus been approved by the US Food and Drug Administration to cure patients with lung, breast, and pancreatic cancers. [13,14] Tamoxifen, a selective ER modulator, is extensively used to cure ER-positive breast cancer. Despite the benefits of tamoxifen, it shows estrogen-like effects in the endometrium and increases the ratio of EC.…”

Section: Introductionmentioning

confidence: 99%

Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/β‐catenin signaling pathways

Karaca

Yerer

Cumaoğlu

et al. 2021

J Biochem & Molecular Tox

View full text Add to dashboard Cite

ERα and Wnt/β-catenin pathways are critical for the progression of most endometrial cancers. We aimed to investigate the cytotoxic and apoptotic effects of tamoxifen and quinazoline derivative drugs of doxazosin and erlotinib, and their roles in ERα and Wnt/β-catenin signaling pathways in human endometrial cancer RL 95-2 cell. 3-(4,5-Dimethylthiazol-2yl)−2,5-diphenyltetrazolium bromide assay and xCEL-Ligence systems were performed to evaluate cytotoxicity. Furthermore, apoptotic induction was tested by Annexin V analysis. Caspase-3 and -9 activity and changes in the mitochondrial membrane potential were evaluated. The level of reactive oxygen species was measured by incubating with dichlorofluorescein diacetate. Protein ratios of p-ERα/ERα, GSK3β/p-GSK3β, and p-β-catenin/β-catenin and expression levels of ESR1, EGFR, c-Myc genes were evaluated to elucidate mechanisms in signaling pathways. We found that the tested drugs showed cytotoxic and apoptotic effects in the cells. Doxazosin significantly reduced ESR1 expression, slightly reduced the p-β-catenin/β-catenin ratio and c-Myc expression. Erlotinib significantly increased c-Myc expression while significantly decreasing the p-β-catenin/β-catenin and p-ERα/ERα ratio, and ESR1 expression. However, we observed that the cells develop resistance to erlotinib over a certain concentration, suggesting that ERα, ESR1, EGFR, and c-Myc may be a new target for overcoming drug resistance in the treatment of endometrial cancer. We also observed that erlotinib and doxazosin play an important role in the ERα signaling pathway and can act as potent inhibitors of PKA and/or tyrosine kinase in the Wnt/β-catenin signaling pathway in RL 95-2 cell.In conclusion, doxazosin and erlotinib may have a possible therapeutic potential in human endometrial cancer.

show abstract

M2013 Effect of Targeting the Neurokinin-1 Receptor On the Transition of Chronic Inflammation to Dysplasia

Cited by 2 publications

References 0 publications

Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies

Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies

Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/β‐catenin signaling pathways

Contact Info

Product

Resources

About