Neferine inhibits epidermal growth factor-induced proliferation and migration of retinal pigment epithelial cells through downregulating p38 MAPK and PI3K/AKT signalling

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dc.authoridGüçlü, Hande/0000-0002-3021-0493
dc.authoridERDOGAN, SUAT/0000-0002-6823-6293
dc.authorwosidOzal, Sadık Altan/B-5123-2019
dc.authorwosidGüçlü, Hande/AAW-9756-2020
dc.contributor.authorOzal, Sadik Altan
dc.contributor.authorGurlu, Vuslat
dc.contributor.authorTurkekul, Kader
dc.contributor.authorGuclu, Hande
dc.contributor.authorErdogan, Suat
dc.date.accessioned2024-06-12T11:09:03Z
dc.date.available2024-06-12T11:09:03Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractPurpose: Proliferative vitreoretinopathy (PVR) occurs in approximately 5-10% of patients after retinal detachment surgery. Neferine is a bis-benzylisoquinoline alkaloid found in the green seed embryos (Nelumbo nucifera) of the lotus flower and has various properties, such as being antithrombotic, antioxidant, neuroprotective, anticancerous, and anti-inflammatory. Although the effects of neferine on the proliferation and migration of cancer cells have been partially shown, their possible role and the mechanism of action on PVR remain unclear. Materials and methods: To mimic a PVR model in vitro, retinal pigment epithelial (RPE) cells were exposed to epidermal growth factor (EGF) and treated with various concentrations of neferine. Cell viability was determined by MTT test. Cell-cycle phase distribution and cell migration were examined by image-based cytometry and wound healing test, respectively. Messenger RNA (mRNA) and protein expression were determined by RT-qPCR and Western blotting, respectively. Results: Stimulation of the cells with EGF significantly increased the rate of proliferation, whilst treatment with low concentrations of neferine-reduced proliferation to a level equal to that seen in untreated cells. Neferine significantly downregulated EGF-increased cell viability, and survivin mRNA expression was depressed to the basal level. In addition, neferine treatment contributed to cell proliferation loss by upregulating p21 and p27 expression leading to cycle arrest at the G1 phase. The treatment significantly inhibited cell migration by upregulating the expression of epithelial markers, such as E-cadherin and occludin, and decreased MMP2, MMP9, alpha-SMA, and vimentin. Neferine treatment markedly reduced phosphotidyl inositol 3-kinase (PI3K), AKT, p-p38 mitogen-activated protein kinase (MAPK), and NF-kappa B (nuclear factor kappa-light-chain-enhancer of activated B cells) protein expression. Conclusion: It can be considered that neferine may be a potential candidate molecule in the treatment of PVR by inhibiting cell proliferation and the migration of EGF-induced RPE cells through the modulation of various transcriptional activities.en_US
dc.description.sponsorshipTrakya University Scientific Research Fund [TUBAP 2018/68]en_US
dc.description.sponsorshipThis study was supported by Trakya University Scientific Research Fund [grant number TUBAP 2018/68].en_US
dc.identifier.doi10.1080/15569527.2020.1730882
dc.identifier.endpage105en_US
dc.identifier.issn1556-9527
dc.identifier.issn1556-9535
dc.identifier.issue2en_US
dc.identifier.pmid32064963en_US
dc.identifier.scopus2-s2.0-85081403387en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage97en_US
dc.identifier.urihttps://doi.org/10.1080/15569527.2020.1730882
dc.identifier.urihttps://hdl.handle.net/20.500.14551/22669
dc.identifier.volume39en_US
dc.identifier.wosWOS:000519169300001en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Ltden_US
dc.relation.ispartofCutaneous And Ocular Toxicologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectNeferineen_US
dc.subjectProliferative Vitreoretinopathyen_US
dc.subjectEpidermal Growth Factoren_US
dc.subjectRetinal Pigment Epithelial Cellen_US
dc.subjectEpithelial-Mesenchymal Transitionen_US
dc.subjectTo-Mesenchymal Transitionen_US
dc.subjectFactor Receptoren_US
dc.subjectVitreoretinopathyen_US
dc.subjectActivationen_US
dc.subjectSurvivalen_US
dc.subjectCycleen_US
dc.subjectManagementen_US
dc.subjectApoptosisen_US
dc.titleNeferine inhibits epidermal growth factor-induced proliferation and migration of retinal pigment epithelial cells through downregulating p38 MAPK and PI3K/AKT signallingen_US
dc.typeArticleen_US

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