scholarly journals Gambogic acid inhibits thioredoxin activity and induces ROS-mediated cell death in castration-resistant prostate cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 77181-77194 ◽  
Author(s):  
Hong Pan ◽  
Keith H. Jansson ◽  
Michael L. Beshiri ◽  
JuanJuan Yin ◽  
Lei Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Gambogic Acid ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Nucleoside antibiochemotherapy repressed the growth, chemoresistance, survival, and metastatic potentials of castration-resistant prostate cancer cells

2021 ◽  
Author(s):  
Saheed Oluwasina Oseni ◽  
Genesis Acosta Laguer ◽  
Faika Ambrin ◽  
Magdalah Philemy ◽  
Javoncia Betty ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Fluorescent Microscopy ◽  
P53 Gene ◽  
Castration Resistant Prostate Cancer ◽  
Migration Assay ◽  
Nucleoside Antibiotics ◽  
Castration Resistant ◽  
Anticancer Effects

ABSTRACTThere is currently no definitive cure for metastatic castration-resistant prostate cancer (mCRPC), therefore justifying the incessant need for more investigative studies to either repurpose old drugs or identify novel and effective therapeutics. In this study, we investigated the possible anticancer effects of two nucleoside antibiotics: puromycin and blasticidin. We hypothesized that the two antibiotics alone or combined with other drugs will inhibit prostate cancer (PCa) cell proliferation and metastasis and induce cell death via apoptosis. mCRPC cell lines (PC3 and DU145) with different p53-gene statuses were cultured and seeded in 96 well-plates, and thereafter treated with varying concentrations of puromycin and blasticidin (1 ng/mL - 100 μg/mL) for 24 - 48 hours. Resazurin reduction and/or MTT assays were done to evaluate the treatment-induced effects on mCRPC cell viability and proliferation. The colony-forming assay measured the cell survival rate following treatment nucleoside antibiotics while scratch migration assay and dual-fluorescent microscopy assessed the effects on metastatic potential and cell death, respectively. The two antibiotics were combined with either paclitaxel, docetaxel, or cabazitaxel to check for synergism. Our results indicate that both antibiotics exhibit dose- and time-dependent anticancer effects on growth, survival, and metastasis of mCRPCs. PC3 cells were significantly more susceptible to both antibiotics compared to DU145 cells. Both cell lines were more susceptible to puromycin compared to blasticidin. Synergism was observed when each antibiotic compound was combined with any of the three taxanes. In conclusion, we have demonstrated that both puromycin and blasticidin could be explored for the treatment of mCRPC.GRAPHICAL ABSTRACT

scholarly journals Castration-resistant prostate cancer: Androgen receptor inactivation induces telomere DNA damage, and damage response inhibition leads to cell death

2019 ◽  
Author(s):  
Vidyavathi Reddy ◽  
Asm Iskander ◽  
Clara Hwang ◽  
George Divine ◽  
Mani Menon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Combined Treatment ◽  
Full Length ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Damage Response

AbstractTelomere stability is important for cell viability, as cells with telomere DNA damage that is not repaired do not survive. We reported previously that androgen receptor (AR) antagonist induces telomere DNA damage in androgen-sensitive LNCaP prostate cancer cells; this triggers a DNA damage response (DDR) at telomeres that includes activation of ATM, and blocking ATM activation prevents telomere DNA repair and leads to cell death. Remarkably, AR antagonist induces telomere DNA damage and triggers ATM activation at telomeres also in 22Rv1 castration-resistant prostate cancer (CRPC) cells that are not growth inhibited by AR antagonist. Treatment with AR antagonist enzalutamide (ENZ) or ATM inhibitor (ATMi) by itself had no effect on growth in vitro or in vivo, but combined treatment with ENZ plus ATMi significantly inhibited cell survival in vitro and tumor growth in vivo. By inducing telomere DNA damage and activating a telomere DDR, an opportunity to inhibit DNA repair and promote cell death was created, even in CRPC cells. 22Rv1 cells express both full-length AR and AR splice variant AR-V7, but full-length AR was found to be the predominant form of AR associated with telomeres and required for telomere stability. Although 22Rv1 growth of untreated 22Rv1 cells appears to be driven by AR-V7, it is, ironically, expression of full-length AR that makes them sensitive to growth inhibition by combined treatment with ENZ plus ATMi. Notably, this combined treatment approach to induce telomere DNA damage and inhibit the DDR was effective in inducing cell death also in other CRPC cell lines (LNCaP/AR and C4-2B). Thus, the use of ENZ in combination with a DDR inhibitor, such as ATMi, may be effective in prolonging disease-free survival of patients with AR-positive metastatic CRPC, even those that co-express AR splice variant.

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

2020 ◽  
pp. 096032712098420
Author(s):  
Gamze Guney Eskiler ◽  
Asuman Deveci Ozkan ◽  
Isil Ezgi Eryilmaz ◽  
Unal Egeli ◽  
Gulsah Cecener
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Signaling Pathways ◽  
Apoptotic Cell ◽  
Expression Level ◽  
Toll Like Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Rt Pcr ◽  
Toll Like Receptor 4 ◽  
Castration Resistant

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.

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