Inhibition of Ribonucleotide Reductase Induces Endoplasmic Reticulum Stress and Apoptosis, Leading to the Death of Docetaxel-resistant Prostate Cancer Cells

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dc.authoridSERTTAS, RIZA/0000-0002-7493-0388
dc.authoridERDOGAN, SUAT/0000-0002-6823-6293
dc.authorwosidSERTTAS, RIZA/AAG-7463-2020
dc.contributor.authorSerttas, Riza
dc.contributor.authorErdogan, Suat
dc.date.accessioned2024-06-12T10:52:27Z
dc.date.available2024-06-12T10:52:27Z
dc.date.issued2023
dc.departmentTrakya Üniversitesien_US
dc.description.abstractBackground The development of chemotherapy resistance in prostate cancer (PCa) patients poses a significant obstacle to disease progression. Ribonucleotide reductase is a crucial enzyme for cell division and tumor growth. Triapine, an inhibitor of ribonucleotide reductase, has shown strong anti-tumor activity in various types of cancers. However, the effect of triapine on docetaxel-resistant (DR) human PCa cells has not been explored previously.Aim This study aimed to examine the potential anti-proliferative effects of triapine in PC3-DR (docetaxel-resistant) cells.Methods Cell viability was determined by the MTT test, and apoptosis and cell cycle progression were analyzed by image-based cytometer. mRNA and protein expression were assessed by RT-qPCR and western blot, respectively.Results Triapine administration significantly reduced PC3 and PC3-DR cells' survival, while the cytotoxic effect was higher in PC3-DR cells. Cell death resulting from inhibition of ribonucleotide reductase was mediated by endoplasmic reticulum stress, induction of apoptosis, and cell cycle arrest. The findings were supported by the upregulation of caspases, Bax, Bak, P21, P27, P53, TNF-alpha, FAS, and FASL, and downregulation of Bcl2, Bcl-XL, cyclin-dependent kinase 2 (CDK2), CDK4, cyclins, and heat shock proteins expression. According to the data, the reduction of ABC transporter proteins and NF-kappa B expression may play a role in triapine-mediated cytotoxicity in docetaxel-resistant cells.Conclusion Based on our findings, triapine emerges as a promising chemotherapeutic approach for combating docetaxel-resistant prostate cancer.en_US
dc.description.sponsorshipDeclared none.en_US
dc.description.sponsorshipDeclared none.en_US
dc.identifier.doi10.2174/1871520623666230810094635
dc.identifier.endpage1965en_US
dc.identifier.issn1871-5206
dc.identifier.issn1875-5992
dc.identifier.issue17en_US
dc.identifier.pmid37565554en_US
dc.identifier.scopus2-s2.0-85173773101en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage1958en_US
dc.identifier.urihttps://doi.org/10.2174/1871520623666230810094635
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18692
dc.identifier.volume23en_US
dc.identifier.wosWOS:001090859100007en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherBentham Science Publ Ltden_US
dc.relation.ispartofAnti-Cancer Agents In Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApoptosisen_US
dc.subjectDocetaxelen_US
dc.subjectEndoplasmic Reticulumen_US
dc.subjectProstate Canceren_US
dc.subjectPC3en_US
dc.subjectTriapineen_US
dc.subjectDrug-Resistanceen_US
dc.subjectIn-Vitroen_US
dc.subjectPhase-Ien_US
dc.subjectTriapineen_US
dc.subjectCombinationen_US
dc.subjectChemotherapyen_US
dc.subjectMechanismsen_US
dc.titleInhibition of Ribonucleotide Reductase Induces Endoplasmic Reticulum Stress and Apoptosis, Leading to the Death of Docetaxel-resistant Prostate Cancer Cellsen_US
dc.typeArticleen_US

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