Induction of autophagy enhances apoptotic cell death via epidermal growth factor receptor inhibition by canertinib in cervical cancer 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.authorDere, Egemen
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-08-30T20:06:50Z
dc.date.available2020-08-30T20:06:50Z
dc.date.issued2019
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractBackground: It has been known epidermal growth factor receptor (EGFR) frequently overexpressed in cervical cancer. High levels of EGFR expression in their tumors leads to a poor prognosis and inhibition frequently induces autophagy in cancer cells. This study aimed to investigate whether EGFR inhibition by canertinib induces autophagy and this induction influence the effect of Palladium (Pd) (II) complex and 5-fluorouracil (5-FU) especially in nontoxic doses. Methods: Cytotoxicity was evaluated by using SRB assay. Apoptosis, autophagy, and EGFR key markers were determined by flow cytometry, fluorescence staining, and immunoblotting. Colony formation, invasion, and wound healing assays were performed to investigate cell proliferation, invasion, and migration, respectively. Results: Blocking EGFR by the pan-ErbB tyrosine kinase inhibitor canertinib inhibited cell growth of HeLa cervical cancer cells in combination with Pd(II) complex and 5-FU. Combination of canertinib and Pd(II) complex promotes autophagy and apoptosis of HeLa cancer cells via blockade of the PI3K/AKT and MAPK/ERK pathway, which leads to cervical cancer cell death. ROS accumulation and DNA damage were increased after combinatorial treatment which causes depolarization of the mitochondrial inner membrane and leads to apoptotic cell death. Canertinib combined with Pd(II) complex leads to inhibition of migration and invasion. Conclusion: Inhibition of EGFR signaling by canertinib in combination with Pd(II) complex promotes apoptosis and autophagy via blockade of the PI3K/AKT and MAPK/ERK. General significance: The cytotoxic activity of Pd(II) complex and 5-FU on HeLa cells is mediated by EGFR inhibition and autophagy induction, leading to activation of mitochondrial apoptotic cell death.en_US
dc.description.sponsorshipScientific Research Projects Foundation (BAP) of Uludag University of Turkey; UAP [(F)-2013/43]en_US
dc.description.sponsorshipThe authors would like to thank Prof. Dr. Veysel Turan Yilmaz for providing Pd(II) compound. This study was supported by a grant from the Scientific Research Projects Foundation (BAP) of Uludag University of Turkey [Project No. UAP(F)-2013/43]en_US
dc.identifier.citationAydinlik, S., Dere, E., & Ulukaya, E. (2019). Induction of autophagy enhances apoptotic cell death via epidermal growth factor receptor inhibition by canertinib in cervical cancer cells. Biochimica et Biophysica Acta (BBA)-General Subjects, 1863(5), 903-916.en_US
dc.identifier.doi10.1016/j.bbagen.2019.02.014en_US
dc.identifier.endpage916en_US
dc.identifier.issn0304-4165en_US
dc.identifier.issn1872-8006en_US
dc.identifier.issue5en_US
dc.identifier.pmid30825616en_US
dc.identifier.scopus2-s2.0-85062422942en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage903en_US
dc.identifier.urihttps://doi.org/10.1016/j.bbagen.2019.02.014
dc.identifier.urihttps://hdl.handle.net/20.500.12713/632
dc.identifier.volume1863en_US
dc.identifier.wosWOS:000465054000013en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorUlukaya, Enginen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofBiochimica Et Biophysica Acta-General Subjectsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAutophagyen_US
dc.subjectApoptosisen_US
dc.subjectTyrosine Kinase Inhibitorsen_US
dc.subjectMitochondrial Depolarizationen_US
dc.subjectEpidermal Growth Factor Receptoren_US
dc.titleInduction of autophagy enhances apoptotic cell death via epidermal growth factor receptor inhibition by canertinib in cervical cancer cellsen_US
dc.typeArticleen_US

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