Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line

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dc.authoridEngin Ulukaya / 0000-0003-4875-5472
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.contributor.authorAydınlık, Şeyma
dc.contributor.authorErkısa, Merve
dc.contributor.authorCevatemre, Buse
dc.contributor.authorSarımahmut, Mehmet
dc.contributor.authorDere, Egemen
dc.contributor.authorArı, Ferda
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-08-30T20:08:13Z
dc.date.available2020-08-30T20:08:13Z
dc.date.issued2017
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractBackground: The outcome of triple negative breast cancer is still poor and requires improvement with better therapy options. Autophagy has recently been shown to play a role in anticancer drug resistance. Therefore, we investigated if the effectiveness of doxorubicin was augmented by the inhibition of autophagy. Methods: MDA-MB-231 was used as a model cell line for triple negative breast cancer and 3-methyladenine was used as an inhibitor of autophagy. Cells were treated with 0.46-1.84 mu M doxorubicin and 2.5-10 mu M 3-methyladenine for 48 h. Cell death mode was examined with M30 and M65 ELISA assays. ROS level and LDH activity was examined and the cellular acidic compartment of cells was monitored by acridine orange staining. The expression of various autophagy and apoptosis related proteins/genes were evaluated with Western blotting and RT-qPCR respectively. Results: Synergism was observed between the compounds (CI value < 1.0). RT-qPCR analysis revealed that the combination resulted in a down-regulation of autophagy-related genes. Moreover, the combination resulted in a different cell death modality, upregulating necroptosis-related genes. This suggests that the mode of cell death may switch from apoptosis to necroptosis, which is a more severe form of cell death, when autophagy is inhibited. These results were further confirmed at protein level by Western blotting. Conclusion: Inhibition of autophagy seems to sensitize triple negative breast cancer cells to doxorubicin, warranting further in vivo studies for the proof of this concept. General significance: Autophagy has a key role in drug resistance in MDA-MB-231 cells. Therefore combinatorial approaches may effectively overcome resistance. (C) 2016 Elsevier B.V. All rights reserved.en_US
dc.description.sponsorshipUniversity of UludagUludag University [UAP(F)-2013/43]en_US
dc.description.sponsorshipThe authors thank the Research Fund of University of Uludag for the project numbered UAP(F)-2013/43 for providing the kits/chemicals used in the study.en_US
dc.identifier.citationAydinlik, S., Erkisa, M., Cevatemre, B., Sarimahmut, M., Dere, E., Ari, F., & Ulukaya, E. (2017). Enhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell line. Biochimica et Biophysica Acta (BBA)-General Subjects, 1861(2), 49-57.en_US
dc.identifier.doi10.1016/j.bbagen.2016.11.013en_US
dc.identifier.endpage57en_US
dc.identifier.issn0304-4165en_US
dc.identifier.issn1872-8006en_US
dc.identifier.issue2en_US
dc.identifier.pmid27842219en_US
dc.identifier.scopus2-s2.0-84995553806en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage49en_US
dc.identifier.urihttps://doi.org/10.1016/j.bbagen.2016.11.013
dc.identifier.urihttps://hdl.handle.net/20.500.12713/903
dc.identifier.volume1861en_US
dc.identifier.wosWOS:000392680200005en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorUlukaya, Enginen_US
dc.language.isoenen_US
dc.publisherElsevier Science Bven_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.subjectBreast Canceren_US
dc.subjectNecroptosisen_US
dc.subjectDrug Resistanceen_US
dc.subjectSynergismen_US
dc.titleEnhanced cytotoxic activity of doxorubicin through the inhibition of autophagy in triple negative breast cancer cell lineen_US
dc.typeArticleen_US

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