Pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor increases the efficacy of cabazitaxel by inducing apoptosis and decreasing cancer stem 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.accessioned2024-06-12T10:52:21Z
dc.date.available2024-06-12T10:52:21Z
dc.date.issued2023
dc.departmentTrakya Üniversitesien_US
dc.description.abstractCancer stem cells (CSCs) are associated with metastasis and recurrence in prostate cancer as well as other cancers. We aimed to enhance the sensitivity of cabazitaxel in prostate cancer cell therapy by targeting CSCs with a Wnt inhibitor and salinomycin pretreatment. PC3, DU-145, and LNCaP human prostate cancer cells were exposed to Wnt/beta-catenin pathway inhibitor CCT036477 (iWnt) with salinomycin for 48 h, followed by cabazitaxel treatment for 48 h. Cell viability, mRNA, and protein expression changes were evaluated by MTT, RT-qPCR, and Western blot assays, respectively. Apoptosis was determined by image-based cytometry, and cell migration was assessed by wound healing assay. Three-dimensional culture was established to assess the malignant phenotype and stemness potential of transformed or cancer cells. CD44 + CSCs were isolated using magnetic-activated cell sorting system. Pretreatment of PC3, DU-145, and LNCaP cells with salinomycin iWnt significantly sensitized the cells to cabazitaxel therapy. Spheroid culture confirmed that the treatment modality was more effective than a single administration of chemotherapy. The pretreatment of PC3 cells increased the rate of apoptosis compared to single administration of cabazitaxel, which downregulated Bcl-2 and upregulated caspase 3, caspase 8 expressions. The pretreatment suppressed cell migration, downregulated the expression of Sox2 and Nanog, and significantly reduced CD44 + CSC numbers. Notably, the treatment modality reduced pAKT, p-P38 MAPK, and pERK1/2. The data suggest that pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor may increase the efficacy of cabazitaxel therapy by inhibiting cell proliferation and migration, and eliminating cancer stem cells.en_US
dc.description.sponsorshippreparation of bovine retinal pigment epithelial cellsen_US
dc.description.sponsorshipWe would like to thank Drs. Ruveyde Garip and Sultan Kaya (Trakya University, School of Medicine, Department of Ophthalmology) for their support in the preparation of bovine retinal pigment epithelial cells.en_US
dc.identifier.doi10.1007/s12032-023-02062-1
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue7en_US
dc.identifier.pmid37264204en_US
dc.identifier.scopus2-s2.0-85160914664en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1007/s12032-023-02062-1
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18681
dc.identifier.volume40en_US
dc.identifier.wosWOS:001000365000003en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherHumana Press Incen_US
dc.relation.ispartofMedical Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApoptosisen_US
dc.subjectCabazitaxelen_US
dc.subjectCancer Stem Cellen_US
dc.subjectProstate Canceren_US
dc.subjectSalinomycinen_US
dc.subjectWnt/Beta-Cateninen_US
dc.subjectAngiogenesisen_US
dc.subjectMetastasisen_US
dc.subjectGrowthen_US
dc.subjectEmten_US
dc.titlePretreatment of prostate cancer cells with salinomycin and Wnt inhibitor increases the efficacy of cabazitaxel by inducing apoptosis and decreasing cancer stem cellsen_US
dc.typeArticleen_US

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