A promising therapeutic combination for metastatic prostate cancer: Chloroquine as autophagy inhibitor and palladium(II) barbiturate complex

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dc.authoridNazlıhan Aztopal / 0000-0003-3118-8061en_US
dc.authoridRemzi Okan Akar / 0000-0001-8687-2034en_US
dc.authoridEngin Ulukaya / 0000-0003-4875-5472en_US
dc.authoridMerve Erkısa Genel / 0000-0002-3127-742X
dc.authorscopusidRemzi Okan Akar / 57210603359
dc.authorscopusidNazlıhan Aztopal / 55853882900
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorscopusidMerve Erkısa / 57126208900
dc.authorwosidRemzi Okan Akar / AAF-4576-2019
dc.authorwosidNazlıhan Aztopal / L-6687-2018
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.authorwosidMerve Erkısa / AAM-1001-2020
dc.contributor.authorErkısa Genel, Merve
dc.contributor.authorAydınlık, Şeyma
dc.contributor.authorCevatemre, Buse
dc.contributor.authorAztopal, Nazlıhan
dc.contributor.authorAkar, Remzi Okan
dc.contributor.authorÇelikler, Serap
dc.contributor.authorYılmaz, Veysel Turan
dc.contributor.authorAri, Ferda
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-08-30T20:01:33Z
dc.date.available2020-08-30T20:01:33Z
dc.date.issued2020
dc.departmentİstinye Üniversitesi, Rektörlüken_US
dc.descriptionErkisa Merve (isu author)
dc.descriptionUlukaya Engin (isu author)
dc.description.abstractAutophagy is a catabolic process for cells that can provide energy sources and allows cancer cells to evade cell death. Therefore, studies on the combination of autophagy inhibitors with drugs are increasing as a new treatment modality in cancer. Previously, we reported the anti-tumor activity of a Palladium (Pd)(II) complex against different types of cancer in vitro and in vivo. Chloroquine (CQ), the worldwide used anti-malarial drug, has recently been focused as a chemosensitizer in cancer treatment. The aim of this study was to investigate the efficacy of a combined treatment of these agents that work through different mechanisms to provide an effective treatment modality for metastatic prostate cancer that is certainly fatal. Metastatic prostate cancer cell lines (PC-3 and LNCaP) were treated with Pd (II) complex, CQ, and their combination. The combination enhanced apoptosis by increasing phosphatidylserine translocation and pro-apoptotic proteins. Apoptosis was confirmed by the use of apoptosis inhibitor. The formation of acidic vesicular organelles (AVOs) was observed by acridine orange staining in fluorescence microscopy. The Pd (II) complex increased AVOs formation in prostate cancer cells and CQ-pretreatment has potentiated this effect. Importantly, treatment with CQ suppressed the pro-survival function of autophagy, which might have contributed to enhanced cytotoxicity. In addition, PI3K/AKT/mTOR-related protein expressions were altered after the combination of treatments. Our results suggest that combination treatment enhances apoptotic cell death possibly via the inhibition of autophagy, and may therefore be regarded as a novel and better approach for the treatment of metastatic prostate cancer. © 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)en_US
dc.description.sponsorshipThis work was supported by the Research Fund of Bursa Uludag University for the project that is numbered OUAP(T)-2015/19 .en_US
dc.identifier.citationMerve, E., Aydinlik, S., Cevatemre, B., Aztopal, N., Akar, R. O., Celikler, S., & Engin, U. (2020). A promising therapeutic combination for metastatic prostate cancer: Chloroquine as autophagy inhibitor and palladium (II) barbiturate complex.en_US
dc.identifier.doi10.1016/j.biochi.2020.05.010en_US
dc.identifier.endpage172en_US
dc.identifier.issn0300-9084en_US
dc.identifier.pmid32497551en_US
dc.identifier.scopus2-s2.0-85086773048en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage159en_US
dc.identifier.urihttps://doi.org/10.1016/j.biochi.2020.05.010
dc.identifier.urihttps://hdl.handle.net/20.500.12713/279
dc.identifier.volume175en_US
dc.identifier.wosWOS:000579382300017en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorErkısa Genel, Merveen_US
dc.institutionauthorAztopal, Nazlıhanen_US
dc.institutionauthorAkar, Remzi Okanen_US
dc.institutionauthorUlukaya, Enginen_US
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofBiochimieen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApoptosisen_US
dc.subjectAutophagyen_US
dc.subjectDna Damageen_US
dc.subjectPro-Survivalen_US
dc.titleA promising therapeutic combination for metastatic prostate cancer: Chloroquine as autophagy inhibitor and palladium(II) barbiturate complexen_US
dc.typeArticleen_US

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