Güney, Gamze EskilerÖzkan, Asuman Deveci2024-01-192024-01-192021-07Eskiler, G. G. vd. (2021). ''Association between the anticancer efficacy of cabazitaxel and toll-like receptor 4 mediating signaling pathways in metastatic castration-resistant prostate cancer cells''. Human Experimental Toxicology, 40(7), 1122-1129.0960-32711477-0903https://doi.org/10.1177/0960327120984209https://journals.sagepub.com/doi/pdf/10.1177/0960327120984209https://hdl.handle.net/11452/39180Background: We evaluated the effect of cabazitaxel (CAB) as a third-line taxane on Toll-like receptor 4 (TLR4)-mediated signaling pathways, especially NF-κB activity, in metastatic castration-resistant prostate cancer (mCRPC) cells. Methods: CAB cytotoxicity was determined by WST-1 assay. To assess the relationship between CAB efficacy and TLR4 signaling pathways, RT-PCR, western blot and immunofluorescence analysis were performed. Additionally, CAB-mediated apoptotic cell death was assessed by Annexin V and RT-PCR analysis. Results: Our results demonstrated that CAB exerted considerably cytotoxic and apoptotic effects on PC-3 mCRPC cells (p < 0.05). CAB treatment altered TLR4 expression level in a dose-dependent manner. Furthermore, 1 nM CAB treatment significantly induced NF-κB activity through p65 nuclear localization and increased the expression level of caspase-3, Bax and p53. Interestingly, total apoptotic cell death and IRF3 protein levels were increased at 5 nM concentration of CAB despite a decrease in the levels of both NF-κB and pro-apoptotic genes. Conclusions: Therefore, NF-κB activity may be a potential target for the efficacy of CAB in mCRPC cells.eninfo:eu-repo/semantics/closedAccessApoptosisCabazitaxelMetastatic castration-resistant prostate cancerToxicologyToll-like receptor 4Antineoplastic agentsApoptosisCell survivalCellsCulturedHumansMaleProstatic neoplasmsCastration-resistantSignal transductionTaxoidsToll-like receptor 4Treatment outcomeNF-kB activityArticle0006365187000012-s2.0-850984959391122112940733380212ToxicologySignal Transduction; CBLB502; Myeloid Differentiation Factor 88CabazitaxelCaspase 3Immunoglobulin enhancer binding proteinInterferon regulatory factor 3Lipocortin 5Protein BaxSynaptotagmin IToll like receptor 4Antineoplastic agentTaxoidToll like receptor 4Antineoplastic activityApoptosisArticleBax geneCas 3 geneCastration-resistant prostate cancer cell line; cell deathControlled studyCytotoxicityGene activityGene expressionHumanHuman cellImmunofluorescenceIRF3 geneMetastatic castration resistant prostate cancerNK kB genep65 geneReal time polymerase chain reactionSignal transductionTLR4 geneTumor suppressor geneWestern blottingWST-1 assayCastration resistant prostate cancerCell cultureCell survivalDrug effectMalePathophysiologySignal transductionTreatment outcome