Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway

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dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoridBilir, Ayhan/0009-0009-9399-5927
dc.authoridDoganlar, Oguzhan/0000-0003-2654-7269
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.authorwosidDoğanlar, Oğuzhan/A-2315-2019
dc.contributor.authorErdogan, Suat
dc.contributor.authorTurkekul, Kader
dc.contributor.authorDibirdik, Ilker
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep B.
dc.contributor.authorBilir, Ayhan
dc.contributor.authorOktem, Gulperi
dc.date.accessioned2024-06-12T11:13:20Z
dc.date.available2024-06-12T11:13:20Z
dc.date.issued2018
dc.departmentTrakya Üniversitesien_US
dc.description.abstractAims: To examine the functions of growth factor midkine (MK) and a flavonoid quercetin on survival, apoptosis and migration of prostate cancer (PCa) stem cells (CSCs). Main methods: CD44(+)/CD133(+) and CD44(+) stem cells were isolated from PC3 and LNCaP cells, respectively by magnetic-activated cell sorting system. 3D cell culture was used to evaluate the ability of quercetin, MK siRNA, and the combination of both to inhibit spheroid formation, apoptosis and cell cycle arrest. Image-based cytometer, RT-qPCR, Western blotting and transwell migration assays were performed. Key findings: Quercetin treatment for 24-72 h inhibited PC3 and CD44+/CD133+ stem cell proliferation in a time-and dose-dependent manner. Knockdown of endogenous MK expression significantly suppressed proliferation of CD44(+)/CD133(+) and CD44(+) cells as well as their parent cells. Co-administration of MK siRNA and quercetin reduced the cell survival, induced apoptosis and caused G1 phase cell cycle arrest more effectively than the individual therapy. Knockdown of MK significantly enhanced the inhibitory effect of quercetin on CD44(+)/CD133(+) migration and spheroid formation. In addition, the combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ABCG2 and NF-kappa B. Significance: Quercetin alone exhibited significant cytotoxic effects on CD44(+)/CD133(+). MK plays an important role in the proliferation of CD44(+)/CD133(+) and CD44(+) cells in particular, and quercetin and MK-silencing therapy may be an important strategy in targeting CSCs that play a role in relapse, migration and drug resistance.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [115S356]en_US
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK grant no: 115S356). The author thanks Riza Serttas, Talha Baykul and Mehmet D. Ozdemir for their technical assistance.en_US
dc.identifier.doi10.1016/j.biopha.2018.08.061
dc.identifier.endpage805en_US
dc.identifier.issn0753-3322
dc.identifier.issn1950-6007
dc.identifier.pmid30142541en_US
dc.identifier.scopus2-s2.0-85051826929en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage793en_US
dc.identifier.urihttps://doi.org/10.1016/j.biopha.2018.08.061
dc.identifier.urihttps://hdl.handle.net/20.500.14551/23497
dc.identifier.volume107en_US
dc.identifier.wosWOS:000445036200087en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevieren_US
dc.relation.ispartofBiomedicine & Pharmacotherapyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectQuercetinen_US
dc.subjectProstate Cancer Stem Cellsen_US
dc.subjectPC3en_US
dc.subjectLncapen_US
dc.subjectMidkineen_US
dc.subjectMigrationen_US
dc.subjectBreast-Canceren_US
dc.subjectIn-Vitroen_US
dc.subjectSignaling Pathwayen_US
dc.subjectCycle Arresten_US
dc.subjectExpressionen_US
dc.subjectInhibitionen_US
dc.subjectApoptosisen_US
dc.subjectGrowthen_US
dc.subjectProliferationen_US
dc.subjectResistanceen_US
dc.titleMidkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathwayen_US
dc.typeArticleen_US

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