Palladium (II) complex and thalidomide intercept angiogenic signaling via targeting FAK/Src and Erk/Akt/PLC gamma dependent autophagy pathways in human umbilical vein endothelial cells

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dc.authoridEngin Ulukaya / 0000-0003-4875-5472en_US
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.contributor.authorAydınlık, Şeyma
dc.contributor.authorÜvez, Ayça
dc.contributor.authorKıyan, Hülya Tuba
dc.contributor.authorGürel-Gürevin, Ebru
dc.contributor.authorYılmaz, Veysel Turan
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2021-08-08T08:19:57Z
dc.date.available2021-08-08T08:19:57Z
dc.date.issued2021en_US
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractThe current study assessed the effects of the thalidomide and palladium (II) saccharinate complex of terpyridine on the suppression of angiogenesis-mediated cell proliferation. The viability was assessed after treatment with palladium (II) complex (1.56–100 ?M) and thalidomide (0.1-400 µM) alone by using ATP assay for 48h. Palladium (II) complex was found to inhibit growth statistically significant in a dose-dependent manner in HUVECs and promoted PARP-1 cleavage through the production of ROS. On the other hand, thalidomide did not cause any significant change in cell viability. Moreover, cell death was observed to be manifested as late apoptosis due to Annexin V/SYTOX staining after palladium (II) complex treatment however, thalidomide did not demonstrate similar results. Thalidomide and palladium (II) complex also suppressed HUVEC migration and capillary-like structure tube formation in vitro in a time-dependent manner. Palladium (II) complex (5 mg/ml) treatment showed a strong antiangiogenic effect similar to positive control thalidomide (5mg/ml) and successfully disrupted the vasculature and reduced the thickness of the vessels compared to control (agar). Furthermore, suppression of autophagy enhanced the cell death and antiangiogenic effect of thalidomide and palladium (II) complex. We also showed that being treated with thalidomide and palladium (II) complex inhibited phosphorylation of the signaling regulators downstream of the VEGFR2. These results provide evidence for the regulation of endothelial cell functions that are relevant to angiogenesis through the suppression of the FAK/Src/Akt/ERK1/2 signaling pathway. Our results also indicate that PLC-?1 phosphorylation leads to activation of p-Akt and p-Erk1/2 which cause stimulation on cell proliferation at lower doses. Hence, we demonstrated that palladium (II) and thalidomide can induce cell death via the Erk/Akt/PLC? signaling pathway and that this pathway might be a novel mechanism.en_US
dc.identifier.citationAydinlik, S., Uvez, A., Kiyan, H. T., Gurel-Gurevin, E., Yilmaz, V. T., Ulukaya, E., & Armutak, E. I. (2021). Palladium (II) complex and thalidomide intercept angiogenic signaling via targeting FAK/Src and Erk/Akt/PLCγ dependent autophagy pathways in human umbilical vein endothelial cells. Microvascular research, 104229. Advance online publication. https://doi.org/10.1016/j.mvr.2021.104229en_US
dc.identifier.doi10.1016/j.mvr.2021.104229en_US
dc.identifier.pmid34339726en_US
dc.identifier.scopus2-s2.0-85113198653en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://doi.org/10.1016/j.mvr.2021.104229
dc.identifier.urihttps://hdl.handle.net/20.500.12713/1980
dc.identifier.wosWOS:000697776700017en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorUlukaya, Engin
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal Pre-proofen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectPalladium Complexen_US
dc.subjectAngiogenesisen_US
dc.subjectAutophagyen_US
dc.subjectVEGF Pathwayen_US
dc.subjectHuman Umbilical Vein Endothelial Cells (HUVECs)en_US
dc.subjectChick Chorioallantoic Membrane (CAM)en_US
dc.titlePalladium (II) complex and thalidomide intercept angiogenic signaling via targeting FAK/Src and Erk/Akt/PLC gamma dependent autophagy pathways in human umbilical vein endothelial cellsen_US
dc.title.alternativePalladium (II) complex and thalidomide intercept angiogenic signaling via targeting FAK/Src and Erk/Akt/PLCγ dependent autophagy pathways in human umbilical vein endothelial cellsen_US
dc.typeArticleen_US

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