Doxorubicin-induced senescence promotes resistance to cell death by modulating genes associated with apoptotic and necrotic pathways in prostate cancer DU145 CD133+/CD44+ cells

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dc.authorscopusid57213831341
dc.authorscopusid22952992800
dc.authorscopusid56364984200
dc.authorscopusid56009604300
dc.contributor.authorTatar, C.
dc.contributor.authorAvci, C.B.
dc.contributor.authorAcikgoz, E.
dc.contributor.authorOktem, G.
dc.date.accessioned2024-08-25T18:31:34Z
dc.date.available2024-08-25T18:31:34Z
dc.date.issued2023
dc.departmentEge Üniversitesien_US
dc.description.abstractCancer stem cells (CSCs) are the most important cause of cancer treatment failure. Traditional cancer treatments, such as chemotherapy and radiotherapy, damage healthy cells alongside malignant cells, leading to severe adverse effects. Therefore, inducing cellular senescence without triggering apoptosis, which further damages healthy cells, may be an alternative strategy. However, there is insufficient knowledge regarding senescence induction in CSCs that show resistance to treatment and stemness properties. The present study aims to elucidate the effects of senescence induction on proliferation, cell cycle, and apoptosis in prostate CSCs and non-CSCs. Prostate CSCs were isolated from DU145 cancer cells using the FACS method. Subsequently, senescence induction was performed in RWPE-1, DU145, prostate CSCs, and non-CSCs by using different concentrations of Doxorubicin (DOX). Cellular senescence was detected using the senescence markers SA-?-gal, Ki67, and senescence-associated heterochromatin foci (SAHF). The effects of senescence on cell cycle and apoptosis were evaluated using the Muse Cell Analyzer, and genes in signaling pathways associated with the apoptotic/necrotic pathway were analyzed by real-time PCR. Prostate CSCs were isolated with 95.6 ± 1.4% purity according to CD133+/CD44+ characteristics, and spheroid formation belonging to stem cells was observed. After DOX-induced senescence, we observed morphological changes, SA-?-gal positivity, SAHF, and the lack of Ki67 in senescent cells. Furthermore; we detected G2/M cell cycle arrest and downregulation of various apoptosis-related genes in senescent prostate CSCs. Our results showed that DOX is a potent inducer of senescence for prostate CSCs, inhibits proliferation by arresting the cell cycle, and senescent prostate CSCs develop resistance to apoptosis. © 2023 Elsevier Inc.en_US
dc.description.sponsorshipEge Üniversitesi: TYL-2018-20033en_US
dc.description.sponsorshipThis study was supported by the Ege University Scientific Research Projects Coordination Unit, Turkey . Project Number: TYL-2018-20033 .en_US
dc.identifier.doi10.1016/j.bbrc.2023.09.032
dc.identifier.endpage210en_US
dc.identifier.issn0006-291X
dc.identifier.pmid37748252en_US
dc.identifier.scopus2-s2.0-85171781280en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage194en_US
dc.identifier.urihttps://doi.org/10.1016/j.bbrc.2023.09.032
dc.identifier.urihttps://hdl.handle.net/11454/99952
dc.identifier.volume680en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofBiochemical and Biophysical Research Communicationsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240825_Gen_US
dc.subjectCancer stem cellen_US
dc.subjectCell cycle arresten_US
dc.subjectDoxorubicinen_US
dc.subjectProstate canceren_US
dc.subjectSenescenceen_US
dc.subjectTherapy-induced senescenceen_US
dc.subjectbeta galactosidaseen_US
dc.subjectCD133 antigenen_US
dc.subjectdoxorubicinen_US
dc.subjectHermes antigenen_US
dc.subjectKi 67 antigenen_US
dc.subjectapoptosisen_US
dc.subjectArticleen_US
dc.subjectcancer resistanceen_US
dc.subjectcancer stem cellen_US
dc.subjectcell agingen_US
dc.subjectcell cycleen_US
dc.subjectcell deathen_US
dc.subjectcell isolationen_US
dc.subjectcontrolled studyen_US
dc.subjectdown regulationen_US
dc.subjectDU145 cell lineen_US
dc.subjectG2 phase cell cycle checkpointen_US
dc.subjectgene controlen_US
dc.subjectgenetic associationen_US
dc.subjectheterochromatinen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectmaleen_US
dc.subjectnecrosisen_US
dc.subjectprostate canceren_US
dc.subjectRWPE-1 cell lineen_US
dc.subjectsignal transductionen_US
dc.subjecttumor growthen_US
dc.subjecttumor spheroiden_US
dc.titleDoxorubicin-induced senescence promotes resistance to cell death by modulating genes associated with apoptotic and necrotic pathways in prostate cancer DU145 CD133+/CD44+ cellsen_US
dc.typeArticleen_US

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