The flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-?B signaling

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dc.authoridSERTTAS, RIZA/0000-0002-7493-0388
dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoridBilir, Ayhan/0009-0009-9399-5927
dc.authoridDoganlar, Oguzhan/0000-0003-2654-7269
dc.authoridERDOGAN, SUAT/0000-0002-6823-6293
dc.authoridBILIR, AYHAN/0000-0002-1132-3599
dc.authorwosidSERTTAS, RIZA/AAG-7463-2020
dc.authorwosidDoğanlar, Oğuzhan/A-2315-2019
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.contributor.authorErdogan, Suat
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep B.
dc.contributor.authorSerttas, Riza
dc.contributor.authorTurkekul, Kader
dc.contributor.authorDibirdik, Ilker
dc.contributor.authorBilir, Ayhan
dc.date.accessioned2024-06-12T10:52:19Z
dc.date.available2024-06-12T10:52:19Z
dc.date.issued2016
dc.departmentTrakya Üniversitesien_US
dc.description.abstractAims: Cancer stem cells (CSCs) are involved in drug resistance, metastasis and recurrence of cancers. The efficacy of apigenin on cell survival, apoptosis, migration and stemness properties were analyzed in CSCs. Main methods: Prostate CSCs (CD44(+)) were isolated from human prostate cancer (PCa) PC3 cells using a magnetic-activated cell sorting system. PC3 and CSCs were treated with various concentrations of apigenin, docetaxel and their combinations for 48 h. Key findings: Apigenin dose dependently inhibited CSCs and PC3 cell survival, and this was accompanied with a significant increase of p21 and p27. Apigenin induced apoptosis via an extrinsic caspase-dependent pathway by upregulating the mRNA expressions of caspases-8,-3 and TNF-alpha, but failed to regulate the intrinsic pathway as determined by the Bax, cytochrome c (Cyt-c) and APAF-1 in CSCs. In contrary to CSCs, apigenin induced intrinsic apoptosis pathway as evidenced by the induction of Bax, Cyt-c and caspase-3 while caspase-8, TNF-alpha and Bcl-2 levels remained unchanged in PC3 cells. The flavonoid strongly suppressed the migration rate of CSCs compared to untreated cells. Significant downregulation of matrix metallopeptidases-2,-9, Snail and Slug exhibits the ability of apigenin treatment to suppress invasion. The expressions of NF-kappa B p105/p50, PI3K, Akt and the phosphorylation of pAkt were decreased after apigenin treatment. Moreover, apigenin treatment significantly reduced pluripotency marker Oct3/4 protein expression which might be associated with the down-regulation of PI3K/Akt/NF-kappa B signaling. Significance: Our data indicated that, apigenin could be a useful compound to prevent proliferation and migration of cancer cells as well as CSCs. (C) 2016 Elsevier Inc. All rights reserved.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [115S356]en_US
dc.description.sponsorshipWe would like to thank Dr. S. Spence (Glasgow/UK) for carefully reading and correcting grammar of this manuscript. This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK grant no: 115S356).en_US
dc.identifier.doi10.1016/j.lfs.2016.08.019
dc.identifier.endpage86en_US
dc.identifier.issn0024-3205
dc.identifier.issn1879-0631
dc.identifier.pmid27569589en_US
dc.identifier.scopus2-s2.0-84984646296en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage77en_US
dc.identifier.urihttps://doi.org/10.1016/j.lfs.2016.08.019
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18671
dc.identifier.volume162en_US
dc.identifier.wosWOS:000384632100011en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.ispartofLife Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApigeninen_US
dc.subjectCD44(+)en_US
dc.subjectCscsen_US
dc.subjectDocetaxelen_US
dc.subjectPC3en_US
dc.subjectProstate Canceren_US
dc.subjectStem Cellsen_US
dc.subjectDown-Regulationen_US
dc.subjectCycle Arresten_US
dc.subjectMatrix Metalloproteinasesen_US
dc.subjectGene-Expressionen_US
dc.subjectPc-3 Cellsen_US
dc.subjectApoptosisen_US
dc.subjectInhibitionen_US
dc.subjectInvasionen_US
dc.subjectPathwayen_US
dc.subjectModulationen_US
dc.titleThe flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-?B signalingen_US
dc.typeArticleen_US

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