Search

Prostate cancer is a common type of cancer in men with high incidence and mortality. Our aim was to investigate the effects of oxalipalladium (ox-Pd) on metastatic human prostate cancer PC3 cells and compare them with the effects of oxaliplatin (ox-Pt) (as an approved cancer drug). We synthesized ox-Pd through a new chemical method and used FT-IR, 1 H NMR, 13 C NMR, and MS analyzes to characterize it. The effects of ox-Pd on PC3 cells viability, apoptosis, cell cycle, migration, and gene expression were examined. Inhibition of topoisomerase IIα activity was investigated by pHOT1 plasmid relaxation and kDNA decatenation assays. Chemical tests showed ox-Pd with the correct composition and structure. For the first time, the exact fragmentation pathway of ox-Pd and its difference with ox-Pt was obtained by MS analysis. Ox-Pd significantly decreased PC3 cell viability with less/no toxicity effect on MHFB-1 normal skin fibroblasts. Wound scratch assay confirmed the strong anti-migratory activity of ox-Pd. According to flow cytometry analysis, this drug increased the number of PC3 cells in late apoptosis and decreased DNA replication and mitosis. Furthermore, pHOT1 plasmid relaxation and kDNA decatenation assays showed that ox-Pd strongly inhibited the catalytic activity of topoisomerase IIα. The expression of topoisomerase IIα, Bcl-2, P21, and survivin was decreased while the expression of Bax and p53 was increased under ox-Pd treatment. We provide the first evidence that ox-Pd exhibits more selective anticancer effects on PC3 cells compared to ox-Pt. Taken together, these data strongly suggest a therapeutic window for ox-Pd in cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Metastatic castration-resistant prostate cancer is the most dangerous stage of prostate cancer, with a high mortality rate. Docetaxel chemotherapy is one of the most effective treatment methods currently, but some patients do not respond to chemotherapy. To avoid unnecessary toxicity in non-responders, this study explores the potential of circulating microRNAs as early biomarkers of docetaxel response in patients with metastatic castration-resistant prostate cancer. Methods: PC3 cells and DU145 cells were divided into the control, NC mimics, and miRNA-136-5p-mimics groups. Cell viability was measured using the CCK-8 assay. Cell apoptosis was determined by flow cytometry. Cell migration and invasion abilities were evaluated using the Transwell assay. Real-time quantitative PCR was used to measure the miRNA levels in cells and peripheral blood of patients. The miRNA-136-5p target genes were predicted by using the PITA, TargetScan, and miRanda databases. The target genes were analyzed with KEGG pathway analysis. Results: In both PC3 and DU145 cells, the miRNA-136-5p-mimics group exhibited significantly increased cell survival rates, migration and invasion numbers, and significantly decreased apoptosis rates than the control group (p < 0.05). The miRNA-222-3p and miRNA-136-5p levels were significantly increased in docetaxel-resistant PC3 and DU145 cells (p < 0.05). The levels of circulating miRNA-222-3p and miRNA-136-5p were significantly associated with docetaxel treatment (p < 0.05). Higher levels of miRNA-222-3p were observed in non-responsive patients (p < 0.05). The area under the curve for miRNA-222-3p was 0.76 (95%CI: 0.55–0.97), indicating its effectiveness as a predictive factor for non-responsive patients to docetaxel. Patients with high expression of miRNA-34c-5p after docetaxel chemotherapy had shorter overall survival times (P < 0.05). Bioinformatics analysis identified 110 potential target genes of miRNA-136-5p. KEGG revealed that these genes were mainly distributed in three pathways. Among them, the PI3K-AKT pathway was closely related to the metastasis of prostate cancer cells. Conclusion: Our study demonstrates that miRNA-136-5p promotes the proliferation and invasion of PC3 and DU145 cells while inhibiting apoptosis. Circulating miRNA-222-3p may serve as a biomarker for early therapeutic response to docetaxel, and further clinical investigation is warranted. Additionally, miRNA-136-5p may have anti-cancer effects during docetaxel chemotherapy in metastatic castration-resistant prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Metastatic castration-resistant prostate cancer is the most dangerous stage of prostate cancer, with a high mortality rate. Docetaxel chemotherapy is one of the most effective treatment methods currently, but some patients do not respond to chemotherapy. To avoid unnecessary toxicity in non-responders, this study explores the potential of circulating microRNAs as early biomarkers of docetaxel response in patients with metastatic castration-resistant prostate cancer. Methods PC3 cells and DU145 cells were divided into the control, NC mimics, and miRNA-136-5p-mimics groups. Cell viability was measured using the CCK-8 assay. Cell apoptosis was determined by flow cytometry. Cell migration and invasion abilities were evaluated using the Transwell assay. Real-time quantitative PCR was used to measure the miRNA levels in cells and peripheral blood of patients. The miRNA-136-5p target genes were predicted by using the PITA, TargetScan, and miRanda databases. The target genes were analyzed with KEGG pathway analysis. Results In both PC3 and DU145 cells, the miRNA-136-5p-mimics group exhibited significantly increased cell survival rates, migration and invasion numbers, and significantly decreased apoptosis rates than the control group (p

Prostate cancer (PCa) poses a serious burden to men. Interferon-β (IFN-β) is implicated in cancer cell growth. This study hence explored the regulation of IFN-β-modified human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in PCa cells. In vitro-cultured hUCMSCs were transfected with pcDNA3.1-IFN-β plasmid or IFN-β siRNA. hUCMSC-Exos were extracted by ultracentrifugation and identified. PCa cells (PC3 and LNCap) were treated with Exos. Cellular internalization of Exos by cells was detected by uptake assay. Cell proliferation, cycle, and apoptosis were evaluated by CCK-8, EdU staining, and flow cytometry. Levels of cell cycle-related proteins (cyclin D/cyclin E) were determined by Western blot. The effect of IFN-β-modified hUCMSC-Exos in vivo was analyzed. IFN-β-modified hUCMSC-Exos (Exooe-IFN-β or Exosi-IFN-β) were successfully isolated. IFN-β was encapsulated in Exos, and PCa cells could uptake Exos. After treating with Exooe-IFN-β, PCa cell proliferation was impeded, the percentage of cells in the G0/G1 phase, cyclin D/cyclin E levels, and cell apoptotic rate were elevated, while cells treated with Exooe-IFN-β exhibited contrary trends. IFN-β-modified hUCMSC-Exos reduced PCa tumor size and weight in vivo. Conjointly, IFN-β-modified hUCMSC-Exos suppress PCa cell proliferation and facilitate apoptosis. [ABSTRACT FROM AUTHOR]

ABSTRACTProstate cancer (PCa) poses a serious burden to men. Interferon-β (IFN-β) is implicated in cancer cell growth. This study hence explored the regulation of IFN-β-modified human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in PCa cells. In vitro-cultured hUCMSCs were transfected with pcDNA3.1-IFN-β plasmid or IFN-β siRNA. hUCMSC-Exos were extracted by ultracentrifugation and identified. PCa cells (PC3 and LNCap) were treated with Exos. Cellular internalization of Exos by cells was detected by uptake assay. Cell proliferation, cycle, and apoptosis were evaluated by CCK-8, EdU staining, and flow cytometry. Levels of cell cycle-related proteins (cyclin D/cyclin E) were determined by Western blot. The effect of IFN-β-modified hUCMSC-Exos in vivo was analyzed. IFN-β-modified hUCMSC-Exos (Exooe-IFN−β or Exosi-IFN−β) were successfully isolated. IFN-β was encapsulated in Exos, and PCa cells could uptake Exos. After treating with Exooe-IFN−β, PCa cell proliferation was impeded, the percentage of cells in the G0/G1 phase, cyclin D/cyclin E levels, and cell apoptotic rate were elevated, while cells treated with Exooe-IFN−β exhibited contrary trends. IFN-β-modified hUCMSC-Exos reduced PCa tumor size and weight in vivo. Conjointly, IFN-β-modified hUCMSC-Exos suppress PCa cell proliferation and facilitate apoptosis.

Surfactant Protein D (SP-D), a pattern recognition innate immune molecule, has been implicated in the immune surveillance against cancer. A recent report showed an association of decreased SP-D expression in human prostate adenocarcinoma with an increased Gleason score and severity. In the present study, the SP-D expression was evaluated in primary prostate epithelial cells (PrEC) and prostate cancer cell lines. LNCaP, an androgen dependent prostate cancer cell line, exhibited significantly lower mRNA and protein levels of SP-D than PrEC and the androgen independent cell lines (PC3 and DU145). A recombinant fragment of human SP-D, rfhSP-D, showed a dose and time dependent binding to prostate cancer cells via its carbohydrate recognition domain. This study, for the first time, provides evidence of significant and specific cell death of tumor cells in rfhSP-D treated explants as well as primary tumor cells isolated from tissue biopsies of metatstatic prostate cancer patients. Viability of PrEC was not altered by rfhSP-D. Treated LNCaP (p53+/+) and PC3 (p53 −/−) cells exhibited reduced cell viability in a dose and time dependent manner and were arrested in G2/M and G1/G0 phase of the cell cycle, respectively. rfhSP-D treated LNCaP cells showed a significant upregulation of p53 whereas a significant downregulation of pAkt was observed in both PC3 and LNCaP cell lines. The rfhSP-D-induced apoptosis signaling cascade involved upregulation of Bax:Bcl2 ratio, cytochrome c and cleaved products of caspase 7. The study concludes that rfhSP-D induces apoptosis in prostate tumor explants as well as in androgen dependent and independent prostate cancer cells via p53 and pAkt pathways.

Surfactant Protein D (SP-D), a pattern recognition innate immune molecule, has been implicated in the immune surveillance against cancer. A recent report showed an association of decreased SP-D expression in human prostate adenocarcinoma with an increased Gleason score and severity. In the present study, the SP-D expression was evaluated in primary prostate epithelial cells (PrEC) and prostate cancer cell lines. LNCaP, an androgen dependent prostate cancer cell line, exhibited significantly lower mRNA and protein levels of SP-D than PrEC and the androgen independent cell lines (PC3 and DU145). A recombinant fragment of human SP-D, rfhSP-D, showed a dose and time dependent binding to prostate cancer cells via its carbohydrate recognition domain. This study, for the first time, provides evidence of significant and specific cell death of tumor cells in rfhSP-D treated explants as well as primary tumor cells isolated from tissue biopsies of metatstatic prostate cancer patients. Viability of PrEC was not altered by rfhSP-D. Treated LNCaP (p53+/+) and PC3 (p53 −/−) cells exhibited reduced cell viability in a dose and time dependent manner and were arrested in G2/M and G1/G0 phase of the cell cycle, respectively. rfhSP-D treated LNCaP cells showed a significant upregulation of p53 whereas a significant downregulation of pAkt was observed in both PC3 and LNCaP cell lines. The rfhSP-D-induced apoptosis signaling cascade involved upregulation of Bax:Bcl2 ratio, cytochrome c and cleaved products of caspase 7. The study concludes that rfhSP-D induces apoptosis in prostate tumor explants as well as in androgen dependent and independent prostate cancer cells via p53 and pAkt pathways. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: One of the most common malignancies among men is prostate cancer. Ellagic acid (EA), a polyphenol antioxidant, has many pharmacological actions, especially anticancer effects. The purpose of this study was to evaluate the effect of EA treatment on interleukin-6 (IL-6) gene expression, cell viability, IL-6 secretion, phosphorylated STAT3, ERK, and AKT cellular signaling proteins in human prostate cancer cells (PC3).Materials and Methods: The cytotoxic effects of the EA (0-100 µM) on PC3 cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. IL-6 gene expression was down, using real-time quantitative polymerase chain reaction. The cellular concentration of phosphorylated ERK1/2, AKT, and STAT3 signaling pathways was assessed by Western blotting technic.Results: EA treatment of PC3 cells resulted in a reduction of cell viability and phosphorylated STAT3, ERK, and AKT signaling proteins after 72 h in a dose-dependent manner. IL-6 gene expression and IL-6 levels significantly increased (P < 0.05) in a dose-dependent pattern in treated PC3 with EA. Thus, these data suggested the essential role of signaling proteins in EA-mediated anti-proliferation of PC3 cells.Conclusions: Our finding shows that EA can be considered as a potent agent that decreases cell proliferation through a reduction of phosphorylated STAT3, ERK, and AKT cellular signaling proteins. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of cancer grows annually worldwide and in Brazil it is the second cause of death. The search for anti-cancer drugs has then become urgent. It depends on the studies of natural and chemical synthesis products. The antitumor action of LQB-118, a pterocarpanquinone structurally related to lapachol, has been demonstrated to induce mechanisms linked to leukemia cell apoptosis. This work investigated some mechanisms of the in vitro antitumor action of LQB-118 on prostate cancer cells. LQB-118 reduced the expression of the c-Myc transcription factor, downregulated the cyclin D1 and cyclin B1 mRNA levels and upregulated the p21 cell cycle inhibitor. These effects resulted in cell cycle arrest in the S and G2/M phases and inhibition of tumor cell proliferation. LQB-118 also induced programmed cell death of the prostate cancer cells, as evidenced by internucleosomal DNA fragmentation and annexin-V positive cells. Except the cell cycle arrest in the S phase and enhanced c-Myc expression, all the mechanisms observed here for the in vitro antitumor action of LQB-118 were also found for Paclitaxel, a traditional antineoplastic drug. These findings suggest new molecular mechanisms for the LQB-118 in vitro antitumor action. [Copyright &y& Elsevier]

AbstractAim:To investigate the cytotoxic effects of four cyclic bisbibenzyls, Riccardin C (Ric), Pakyonol (Pak), Marchantin M (Mar), and Plagiochin E (Pla) against chemoresistant prostate cancer PC3 cells.Methods:Cell growth was assayed by MTT method, and apoptotic related protein Bcl-2 and Bax, poly(ADP-ribose) polymerase (PARP) were examined by Western blotting. Cell cycle and apoptosis of PC3 cells were evaluated with flow cytometry and morphologic examinations.Results:The four compounds inhibited proliferation and elicited cell death in a dose- and time-dependent manner with IC50 values of 3.22 μmol/L for Ric, 7.98 μmol/L for Pak, 5.45 μmol/L for Mar, and 5.99 μmol/L for Pla, respectively. Furthermore, exposed to these chemicals caused a decrease in the antiapoptotic protein Bcl-2 and an increase in proapoptotic Bax expression. PARP cleavage and caspase-3 activity were also observed.Conclusion:The results suggest that cyclic bisbibenzyls could be used for the development of novel therapeutic chemicals against prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: The antidepressant desipramine has been shown to induce a rise in cytosolic Ca2+ levels ([Ca2+]i) and cytotoxicity in human PC3 prostate cancer cells, but the mechanisms underlying its cytotoxic effect is unclear. Cell viability was examined by WST-1 assays. Apoptosis was assessed by propidium iodide staining and an increase in caspase-3 activation. Phosphorylation of protein kinases was analyzed by immunoblotting. Desipramine caused cell death via apoptosis in a concentration-dependent manner. Immunoblotting data revealed that desipramine activated the phosphorylation of c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SP600125 (a selective JNK inhibitor) partially prevented cells from apoptosis. Pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent desipramine-induced [Ca2+]i rises worsened desipramine-induced cytotoxicity. Immunoblotting data suggest that BAPTA/AM pretreatment enhanced desipramine-evoked JNK phosphorylation and caspase-3 cleavage. The results suggest that in PC3 cells, desipramine caused apoptosis via inducing JNK-associated caspase-3 activation, and [Ca2+]i rises may slow down or alleviate desipramine-induced cytotoxicity. [Copyright &y& Elsevier]

Prostate cancer is the most common malignancy and the second leading cause of male death in Western countries. Prostate cancer mortality results from metastases to the bones and lymph nodes and progression from androgen-dependent to androgen-independent disease. Although androgen ablation was found to be effective in treating androgen-dependent prostate cancer, no effective life-prolonging therapy is available for androgen-independent cancer. Epidemiological studies have shown a strong correlation between consumption of cruciferous vegetables and a lower risk of prostate cancer. These vegetables contain glucosinolates, which during metabolism give rise to several breakdown products, mainly indole-3-carbinol (I3C), which may be condensed to polymeric products, especially 3,3'-diindolylmethane (DIM). It was previously shown that these indole derivatives have significant inhibitory effects in several human cancer cell lines, which are exerted through induction of apoptosis. We have previously reported that I3C and DIM induce apoptosis in prostate cancer cell lines through p53-, bax-, bcl-2- and fasL-independent pathways. The objective of this study was examination of the apoptotic pathways that may be involved in the effect of DIM in the androgen-independent prostate cancer cell line, PC3, in vitro. Our results suggest that DIM induces apoptosis in PC3 cells, through the mitochondrial pathway, which involves the translocation of cytochrome c from the mitochondria to the cytosol and the activation of initiator caspase, 9, and effector caspases, 3 and 6, leading to poly ADP-ribose polymerase (PARP) cleavage and induction of apoptosis. Our findings may lead to the development of new therapeutic strategies for the treatment of androgen-independent prostate cancer. [ABSTRACT FROM AUTHOR]