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

Activity of gemcitabine-oxalipaltin (GemOx) plus prednisolone in patients with castration-resistant prostate cancer (CRPC) for whom docetaxel-based chemotherapy failed.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 108-108
Author(s):  
Jae-Lyun Lee ◽  
Yesul Kim ◽  
Jin-Hee Ahn ◽  
MeeKyung Choi ◽  
Seung-Woo Hong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Drug Effects ◽  
Fixed Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3

108 Background: We assessed the cytotoxic effects of the gemcitabine in combination with oxaliplatin (GemOx) in prostate cancer cell lines and evaluated the efficacy and safety of GemOx in patients with metastatic castration-resistant prostate cancer (CRPC) who failed docetaxel based chemotherapy. Methods: Gemcitabine and oxaliplatin were preclinically tested for their cytotoxic activity in LNCaP, PC3 and DU145 cell lines. The combined drug effects were evaluated using the Chou and Taladay analysis. Clinically, patients with CRPC who failed prior docetaxel chemotherapy were treated with gemcitabine 1,000 mg/m2 at fixed-dose rate (10 mg/m2/min) and oxaliplatin 100 mg/m2 intravenously every 2 weeks and prednisolone 5 mg orally twice daily. Unless disease progression or intolerability develops, treatment could be continued until 12 cycles. Primary endpoint was PSA response rate (PCWG 1.0 criteria). Results: The IC50of gemcitabine and oxaliplatin were, respectively, 1.25 μM and 0.69 μM for LNCaP cells; 50.00+ μM and 12.81 μM for PC3 cells; and 11.23 μM and 11.04 μM for DU145 cells. The GemOx combination displayed synergistic effects in all 3 cell lines. In phase II study, 31 patients were accrued. At the time of this analysis 7 patients were still continuing treatment. The median age was 67 years (range 57 ~ 81) and the median dose of docetaxel exposure was 525 mg/m2. A total of 231 cycles administered with a median of 9 cycles per patient. PSA responses were observed in 52% (95% CI, 34~69) and partial responses were observed in 7 of 10 patients with measurable disease. Out of 23 patients, 10 patients achieved pain response (44%). With a median FU duration of 8.0 months, the median time to PSA progression was 6.4 months (95% CI, 3.5~9.2). Peripheral neuropathy developed in 78% of patients but remained of grade 1 ~2 intensities. Frequently observed grade 3 or 4 toxicities were neutropenia (10%), thrombocytopenia (10%), anemia (3%), and diarrhea (3%). Conclusions: GemOx is active and well tolerated in patients with CPRC after docetaxel failure and deserves further investigation in this setting (NCT 01487720). Clinical trial information: NCT01487720.

Statin inhibits the proliferation of human castration-resistant prostate cancer cells by controlling NFkB-LIN28B-let7 miRNA signaling pathway.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 269-269 ◽  
Author(s):  
Chang Wook Jeong ◽  
Ja Hyeon Ku ◽  
Hyeon Hoe Kim ◽  
Cheol Kwak ◽  
Minyong Kang
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Simvastatin Treatment ◽  
Castration Resistant

269 Background: Although statin use has been associated with improved outcomes in prostate cancer, the molecular mechanism of this action is still unclear. Based on previous findings, we aimed to investigate the potential role of NFkB-Lin28B-let7 miRNA signaling pathway in human prostate cancer, particularly, castration-resistant prostate cancer (CRPC) cells, as a molecular mechanism of statin effect. Methods: Various human CRPC cell lines (PC3, DU145, 22Rv1, C42B) were used in this study. Proliferation of prostate cancer cells were measured by MTT assay and colony formation assay. Lin28B and NF-κB expression were controlled by siRNA transfection and the expression on Lin28 and let-7 miRNA were quantitated using RT-PCR and western blotting. Results: Notably, simvastatin treatment on various CRPC cell lines decreased cell viabilities in a dose dependent manner. It also significantly inhibited cell growth in clonogenic assay. In these CRPC cells, LIN28 gene was highly expressed in mRNa and protein levels. Conversely, micro RNA (miRNA) expressions of let7 family were remarkably downregulated in CRPC cells. By simvastatin treatment, mRNA and protein level of Lin28B were decreased, while let7 miRNA expressions were restored, which was the key finding of the current study. Considering NFkB is the upstream molecule of Lin28B, we found that the double treatment of statin and NF-κB inhibitor (CAPE) resulted in decreased cell viability, Lin28B and cyclin D1 expression, synergistically. Of note, let-7 miRNA levels were restored after simvastatin treatment, and further increased their expression levels by CAPE double treatment. In order to confirm this mechanistic clue, we specifically inhibited Lin28B and NF-κB genes, respectively, resulting in increased cell apoptosis signaling in the Lin28b or NF-κB knock down cells by combined treatment with simvastatin. Conclusions: In conclusion, simvastatin inhibited the cell growth of various human CRPC cell lines by controlling NFkB-LIN28B-let7 miRNA signaling pathway, and therefore; concurrent NF-κB inhibition with simvastatin treatment induce the synergistic anti-cancer effects in human CRPC cells.

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 Drug Repurposing of Pantoprazole and Vitamin C Targeting Tumor Microenvironment Conditions Improves Anticancer Effect in Metastatic Castration-Resistant Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhoulei Li ◽  
Peng He ◽  
Yali Long ◽  
Gang Yuan ◽  
Wanqing Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin C ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combined Treatment ◽  
Drug Repurposing ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
18F Fdg

The effective and economical therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) is still requested from patients, who are not available for Lu-177 or Ra-223 treatment. Drug repurposing as a cost-effective and time-saving alternative to traditional drug development has been increasingly discussed. Proton pump inhibitors (PPIs) such as pantroprazole, which are commonly used as antacids, have also been shown to be effective in cancer chemoprevention via induction of apoptosis in multiple cancer cell lines. Vitamin C is an essential micronutrient for human body, has been proposed as a potential anti-cancer agent. In this context, have we investigated the combination of vitamin C and pantoprazole for the management of metastatic castration-resistant prostate cancer (mCRPC). Six chosen human adenocarcinoma cell lines were used to investigate the influence of pantoprazole on the microenvironment of cancer cells (extracellular pH and production of exosomes). Tumor growth and tumor 18F-FDG uptake in PC3 xenografts were analyzed following varied treatment. Our in vitro Results have suggested that pantoprazole enhanced the cytotoxic activity of vitamin C by regulating pH values and production of exosomes in cancer cells. Moreover, the synergistic effect of pantoprazole and vitamin C was pH-dependent since pantoprazole was more effective at a slightly acidic pH. In vivo, the combined treatment using pantoprazole and vitamin C produced better therapeutic outcomes than treatment with vitamin C or pantoprazole alone, as demonstrated via tumor growth and uptake of 18F-FDG. Therefore, we suggest that pantoprazole combined with vitamin C could be as a possible strategy to manage mCRPC.

scholarly journals Development of Novel Chalcone Analogs as Potential Multi-Targeted Therapies for Castration-Resistant Prostate Cancer

2021 ◽  
Author(s):  
Ola Hussein ◽  
Feras Alali ◽  
Ala‐Eddin Al Mustafa ◽  
Ashraf Khalil
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
In Vivo Studies ◽  
Treatment Modalities ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Biological Studies ◽  
In Silico Admet

Prostate cancer (PCa) is the second most frequently diagnosed malignancy, as well as a leading cause of cancer-related mortality in men globally. Despite the initial response to hormonal targeted therapy, the majority of patients ultimately progress to a lethal form of the disease, castration-resistant prostate cancer (CRPC). Therefore, the objective of this study was to discover and develop novel treatment modalities for CRPC. Chalcones are among the highly attractive scaffolds being investigated for their antitumor activities. A library of 26 chalcone analogs were designed, synthesized and evaluated as potential therapies for CRPC. The design was guided by in-silico ADMET prediction in which analogs with favorable drug-likeness properties were prioritized. The new compounds were synthesized, purified and characterized by extensive structural elucidation studies. The compounds in vitro cytotoxicity was evaluated against two androgen receptor (AR)-negative prostate cancer cell lines (PC3 and DU145). Among the tested compounds, pyridine containing analogs (13, 15 and 16) showed potent antiproliferative activities with IC50 values ranging between 4.32-6.47 µM against PC3 and DU145 cell lines. Detailed biological studies of the lead molecule 16 revealed that it can significantly induce apoptosis through upregulation of Bax and downregulation of Bcl-2. In addition, compound 16 potently inhibited colony formation and reduced cell migration of AR-negative PCa cell lines (PC3 and DU145). The molecular pathway analysis showed that the anticancer activity of compound 16 is associated with blocking of ERK1/2 and Akt activities. Furthermore, compound 16 inhibited angiogenesis in the chick chorioallantoic membrane (CAM) model as compared to control. Structure-activity relationship study revealed that the cytotoxicity could dramatically improve via changing the methoxylation pattern by more than 2-folds (IC50 << 2.5 μM). These results indicate that pyridine-based chalcones could serve as promising lead molecules for the treatment of CRPC; thus, further in vitro and in vivo studies are warranted.

Radium-223 therapy in Metastatic Castration-Resistant Prostate Cancer: effects on tumor and normal cell lines

2019 ◽  
Vol 29 (Supplement_1) ◽  
Author(s):  
G Balteiro ◽  
I Marques ◽  
M Abrantes ◽  
A Neves ◽  
I Meireles ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Normal Cell ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223
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