Association between the anticancer efficacy of cabazitaxel and toll-like receptor 4 mediating signaling pathways in metastatic castration-resistant prostate cancer cells. (July 2021)

• Record Type: Journal Article
• Authors: Guney Eskiler, Gamze; Ozkan, Asuman Deveci; Eryilmaz, Isil Ezgi; Egeli, Unal; Cecener, Gulsah
• Is Part Of: Human & experimental toxicology. Volume 40:Number 7(2021)
• Page Start: 1122
• Page End: 1129
• Publication Date: 2021-07
• Subjects: Metastatic castration-resistant prostate cancer -- cabazitaxel -- toll-like receptor 4 -- NF-κB activity -- apoptosis; Toxicology -- Periodicals; 615.9
• DOI: 10.1177/0960327120984209
• Languages: English
• ISSNs: 0960-3271

Abstract

Background: 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.