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The synthesis of nanomaterials using plant extracts is considered to be a safer, environmentally friendly, and cost‐effective alternative method. In this work, Eysenhardtia polystachya (EP) extract and choline chloride/urea (ChCl/urea)‐based deep eutectic solvent (DES) were used for the synthesis of gold nanoparticles (AuNPs), without an additional stabilizing agent, which is of great interest in the field of biomedicine. The antioxidant capacity of the extract and the phenolic content, involved in the reduction of Au3+ ions of the precursor were evaluated. The AuNPs were characterized by ultraviolet‐visible spectroscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, dynamic light scattering, ζ‐potential, confocal laser scanning microscopy, scanning and transmission electron microscopy. The nanoparticles are mostly quasi‐spherical shape, with a multiply‐twinned structure, an average particle size of 36 nm, and a characteristic absorption peak at 545 nm. The colloidal stability was confirmed with a ζ‐potential value of −32.8 mV. Finally, the AuNPs were tested for their potential in cancer therapy using human prostate adenocarcinoma PC‐3 cells. The anti‐inflammatory activity of the EP extract and AuNPs was also evaluated. The results showed that the synthesized AuNPs could potentially induce cell death and have an anti‐inflammatory effect. [ABSTRACT FROM AUTHOR]

Introduction: Regucalcin plays a multifunctional role in the regulation of cellular function including metabolism, signaling process, and transcriptional activity in maintaining cell homeostasis. Downregulated expression or activity of regucalcin contributes to the development of malignancies in various types of human cancer. Survival of cancer patients, including metastatic prostate cancer, is prolonged with high expression of regucalcin in the tumor tissues. Methods: We elucidate whether extracellular regucalcin conquers the growth, migration, invasion, and adhesion of metastatic human prostate cancer PC-3 and DU-145 cells. Results: Extracellular regucalcin (0.1, 1, and 10 nM) of physiologic levels (1 nM at human serum) inhibited colony formation and growth of PC-3 and DU-145 cells, while it did not have an effect on cell death. Repressive effects of extracellular regucalcin on the proliferation were not exhibited by the presence of inhibitors of the cell cycle, intracellular signaling process, and transcriptional activity, suggesting that the signals of extracellular regucalcin are transmitted to block cell growth. Furthermore, extracellular regucalcin (0.1, 1, or 10 nM) inhibited migration, invasion, and adhesion of PC-3 and DU-145 cells. Mechanistically, extracellular regucalcin (10 nM) decreased the levels of various signaling proteins including Ras, posphatidylinositol-3 kinase, mitogen-activated protein kinase, mechanistic target of rapamycin, RSK-2, caveolin-1, and integrin β1 in PC-3 cells. Discussion and Conclusion: Thus, extracellular regucalcin may play a suppressive role in growth, migration, invasion, and adhesion, which are involved in the metastatic activity of human prostate cancer cells, via affecting diverse signaling processes. This study may provide a new strategy in preventing metastatic prostate cancer with exogenous regucalcin. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is addressed as the second most common form of onco-threat worldwide and is usually considered as the major cause of mortality in men. Recent times have seen a surge in exploration of plant-derived components for alternative therapeutical interventions against different oncological malignancies. Dammarolic acid or Asiatic acid (AsA) is an aglycone asiaticoside that has been reported for its efficacy in several ailments including cancer. The current study aimed to investigate the anti-proliferative potency of AsA against human prostate cancer PC-3 cells. Purified AsA was diluted and PC-3 cells were exposed to 20, 40, and 80 µM concentration and incubated for 24 h. Post-exposure, PC-3 cells showcased a substantial loss of their viability at 20 µM (p < 0.05), moreover, this reduction in cell viability escalated proportionally with an increase in AsA at concentrations of 40 and 80 µM (p < 0.01; p < 0.001) respectively. AsA-impelled loss of cellular viability was also evident from the acridine orange-stained photomicrographs, which was also used to quantify the viable and apoptotic cells using Image J software. Additionally, quantification of ROS within PC-3 cells also exhibited an increase in DCF-DA-mediated fluorescence intensity post-exposure to AsA in a dose-dependent manner. AsA-induced apoptosis in PC-3 cells was shown to be associated with augmented activity of caspase-3 proportionally to the AsA concentrations. Thus, initially, this exploratory study explicated that AsA treatment leads to anti-proliferative effects in PC-3 cells by enhancing oxidative stress and inciting apoptosis en route to onset of nuclear fragmentation.

Objective: To observe the expression level of long non-coding RNA FLJ26245 (lncRNA FLJ26245) in prostate cancer tissues and cells, and to explore its effect on the proliferation and migration of prostate cancer PC-3 cells and the underlying mechanism. Methods: A total of 52 pairs of prostate cancer tissues and corresponding para-cancerous tissues from patients who underwent surgery at Luoyang Central Hospital from March 2017 to May 2019 were collected for this study; in addtion, the prostate cancer cell lines (LNCaP, C4-2B, PC-3, DU-145) and normal prostate epithelial cells (RWPE-1) were also selected. qPCR was used to detect the expression level of FLJ26245 in prostate cancer tissues and cells. FLJ26245 mimics and negative control plasmids (lncR-NC) were transfected into PC-3 cells, respectively. MTT assay and Wound-healing test were used to detect the proliferation and migration ability of prostate cancer cells. Bioinformatics technology was used to predict the targeting relationship among FLJ26245, miR-200a-3p, and tyrosine phosphatase receptor G (PTPRG), which was further validated with Dual luciferase reporter gene assay. qPCR and WB methods were used to detect the expression of FLJ26245 downstream gene and proliferation and migration related proteins, respectively. Results: Compared with para-cancerous tissues, the expression level of FLJ26245 in prostate cancer tissues was significantly downregulaed (P<0.01). Compared with RWPE-1 cells, the expression level of FLJ26245 in prostate cancer cells was also significantly decreased (P<0.01 or P<0.05), with the lowest expression in PC-3 cells (P<0.01). Overexpression of FLJ26245 could significantly inhibit the proliferation and migration ability of PC-3 cells (P<0.05 or P<0.01). FLJ26245 could bind to miR-200a-3p, and miR-200a-3p could bind to PTPRG (all P<0.01). After overexpression of FLJ26245, the expression of miR-200a-3p in PC-3 cells was significantly decreased (P<0.01), the mRNA and protein expressions of PTPRG were significantly increased (all P<0.01), and proliferation and migration related proteins, such as cyclin A, CDK2 and Twist, N-cadherin, were significantly reduced (all P<0.01). Conclusion: FLJ26245 is low expressed in prostate cancer tissues and cells. FLJ26245 may inhibit the proliferation and migration of prostate cancer PC-3 cells by regulating the miR-200a-3p/PTPRG axis. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequently diagnosed cancer among men. However, the major modifiable risk factors for PCa are poorly known and its specific mechanism of progression remains unclear. Here we reported that, in prostate cancer cells, the autophagy level was elevated under hypoxic condition, as well as the mRNA and protein level of ATG5, which is an important gene related to autophagy. Furthermore, we found HIF1α could directly bind to the promoter of ATG5 and promote the expression of ATG5 on transcriptional level by luciferase assay and ChIP assay. Intriguingly, overexpression of HIF1α by HIF1α-M could increase tumor size and the effect could be abolished by knockdown ATG5 by si-ATG5 in BALB/cA-nu/nu nude mice. Importantly, HIF1α could also promote the metastasis of PC-3 cells by upregulating the ATG5 and autophagy level and knockdown ATG5 and inhibition autophagy both could abolish the effect of overexpression of HIF1α on the migration of PC-3 cells. Taken together, our results, for the first time, proved that HIF1α could promote the proliferation and migration of PC-3 cells by direct upregulating ATG5 and autophagy level in PC-3 prostate cancer cells. Our findings not only provide new perspective for the relationship between hypoxia and autophagy, but also add new potential therapeutic regimens for the treatment of prostate cancers.

Prostate cancer, which is a bone metastatic cancer, is the second leading cause of cancer-related death in men. There is no effective treatment for metastatic prostate cancer. Regucalcin has been shown to contribute as a suppressor in various types of human cancers. In the present study, furthermore, we investigate an involvement of regucalcin in suppression of prostate cancer. Regucalcin expression was compared in 131 primary tumor tissues and 19 metastatic tumor tissues in prostate cancer patients. Regucalcin expression in the metastatic tumor was found to be reduced as compared with that in primary tumor. The progression-free survival rate was prolonged in patients with a higher regucalcin expression. Translationally, overexpression of regucalcin in bone metastatic human prostate cancer PC-3 and DU-145 cells suppressed colony formation and cell growth in vitro. Mechanistically, overexpressed regucalcin enhanced the levels of p53, Rb, and p21, and decreased the levels of Ras, PI3 kinase, Akt, and mitogen-activated protein kinase, leading to suppression of cell growth. Furthermore, higher regucalcin expression suppressed the levels of nuclear factor-κB p65, β-catenin, and signal transducer and activator of transcription 3, which regulate a transcription activity. Cell growth was promoted by culturing with the calcium agonist Bay K 8644. This effect was blocked by overexpression of regucalcin. Notably, overexpressed regucalcin suppressed bone metastatic activity of PC-3 and DU-145 cells when cocultured with preosteoblastic or preosteoclastic cells. Regucalcin may suppress the development of human prostate cancer, suggesting that gene delivery systems in which its expression is forced may be a novel therapeutic strategy.

Objective: Pomegranate extract gallic acid inhibits the proliferation of prostate cancer PC-3 cells by promoting IGFBP7 expression. Methods: PC-3 cells were divided into six groups: control group (NC), blank control group (BL), IGFBP7 overexpression group (IGFBP7), Pomegranate extract gallic acid group (5.0 µmol/L, 10.0 μmol/L, 20.0 µmol/L). Cell proliferation was detected by MTT assay; apoptosis of each group was analyzed by flow cytometry; the expression levels of IGFBP7, AKT and mTOR were assessed by Western blot. Results: The proliferative plural of PC-3 cells in IGFBP7 group and pomegranate gallic acid group were significantly lower than those in NC and BL groups (P < 0.05). The pomegranate gallic acid group showed dose- dependence. The results of Western blot analysis showed that IGFBP7 group and The levels of IGFBP7 in the pomegranate extract gallic acid group were significantly higher than those in the NC and BL groups (P < 0.05), while the levels of AKT and mTOR plural were significantly lower than those in the NC and BL groups (P < 0.05). Pomegranate extract gallic acid showed dose-effect further elaborated within each group. Conclusion: Pomegranate extract gallic acid can inhibit the expression level of AKT/mTOR protein by enhancing the expression level of IGFBP7, thereby inhibiting the AKT/mTOR signaling pathway, the result is an inhibitory effect on the proliferation of prostate cancer PC-3 cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of exosome originated from bone marrow mesenchymal stem cell (BMSCs) on proliferation, migration and invasion of prostate cancer PC-3 cell and its mechanism. Methods: qPCR was used to detect the expression level of miR-21-5p in prostate cancer cell lines. The morphology of exosomes isolated from BMSCs was observed with an electron microscope. Western blotting was used to detect the expressions of exosome surface markers and the epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin). Dual luciferase reporter gene experiment was used to detect the targeted regulation relationship between miR-21-5p and PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2). PC-3 cells were co-cultured with 10 μl BMSCs exosomes suspension (Exo group), transfected with sh-PHLPP2 or antagomiR, then CCK-8 and Transwell experiments were used to detect changes in proliferation, migration and invasion of PC-3 cell. Results: miR-21-5p was highly expressed in prostate cancer PC-3 cell line. The exosomes in the supernatant of BMSCs culture fluid were successfully isolated, and the typical vesicle-like structures of exosomes were observed under transmission electron microscope. Exosomes expressed specific proteins such as CD9, CD63 and CD81. In the Exo group, the proliferation, invasion, migration, as well as the expressions of N-cadherin, Vimentin and miR-21-5p in PC-3 cells were significantly higher than those in the control group (all P<0.05). PHLPP2 is a target gene of miR-21-5p. Compared with the control group, the expression of PHLPP2 in PC-3 cells of Exo group and sh-PHLPP2 group was significantly reduced (0.66±0.09, 0.42±0.05 vs 1.09±0.08, all P<0.01); cell viability, invasion and migration were significantly improved (all P<0.01); and E-cadherin expression level was significantly reduced while N-cadherin and Vimentin expressions were significantly increased (both P<0.05). Conclusion: miR-21-5p is highly expressed in prostate cancer PC-3 cell line. BMSC exosome miR-21-5p can increase the proliferation, migration and invasion ability of PC-3 cells through targeted down-regulation of PHLPP2. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequently diagnosed cancer among men. However, the major modifiable risk factors for PCa are poorly known and its specific mechanism of progression remains unclear. Here we reported that, in prostate cancer cells, the autophagy level was elevated under hypoxic condition, as well as the mRNA and protein level of ATG5, which is an important gene related to autophagy. Furthermore, we found HIF1α could directly bind to the promoter of ATG5 and promote the expression of ATG5 on transcriptional level by luciferase assay and ChIP assay. Intriguingly, overexpression of HIF1α by HIF1α-M could increase tumor size and the effect could be abolished by knockdown ATG5 by si-ATG5 in BALB/cA-nu/nu nude mice. Importantly, HIF1α could also promote the metastasis of PC-3 cells by upregulating the ATG5 and autophagy level and knockdown ATG5 and inhibition autophagy both could abolish the effect of overexpression of HIF1α on the migration of PC-3 cells. Taken together, our results, for the first time, proved that HIF1α could promote the proliferation and migration of PC-3 cells by direct upregulating ATG5 and autophagy level in PC-3 prostate cancer cells. Our findings not only provide new perspective for the relationship between hypoxia and autophagy, but also add new potential therapeutic regimens for the treatment of prostate cancers. [ABSTRACT FROM AUTHOR]

Abstract Prostate cancer (PC) is one of the most common human malignancies, which has been steadily rising among males in many countries. The leucine-rich repeats and immunoglobulin-like domains (LRIG) genes were applied in the prognosis of different types of cancers, including PC. In that case, this study is supposed to investigate the effects of LRIG3 on PC cells. LRIG3 was overexpressed or under-expressed by the rAd and siRNA to determine the effect of LRIG3 on PC and explore the possible mechanism. The mRNA and protein levels of LRIG3 were tested by RT-qPCR and western blot analysis. Cell apoptosis, viability, migration and invasion were measured using MTT assay, flow cytometry and Transwell assay respectively. We observed that LRIG3 mRNA and protein levels were decreased in PC-3 cells. PC-3 cells treated with rAd-LRIG3 exhibited significantly increased cell apoptosis while inhibited viability, adhesion, migration and invasion. However, C4-2 cells treated with siRNA-LRIG3 showed reciprocal results. In conclusion, these data of the current study indicated that overexpressed LRIG3 gene expression might inhibit the viability, adhesion, invasion and migration and promote the apoptosis of PC cells. rAd-mediated LRIG3 may facilitate a novel aspect of the treatment of patients suffering from with PC. [ABSTRACT FROM AUTHOR]

Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life-threatening androgen-resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC-3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC-3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para-PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour-node-metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell-cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated. [ABSTRACT FROM AUTHOR]

Abstract: A novel and simple strategy for improving the voltammetric response of the cells by heat inactivation method had been proposed. By comparing the voltammetric behavior of the intact cell suspension with that of the fragmentized cell suspension, the results indicated that the former was weaker than the latter, and heat inactivation was superior to ultrasonication in improving the voltammetric response of the cells by increasing the release of the intracellulare guanine and xanthine into the cell eluent as a result of fragmenting the cell membrane. The comparison of cytotoxicity evaluations of the PC-3 cells based on the electrochemical method and the MTT assays suggested the antitumor drug sensitivity test based on the electrochemical method was credible, sensitive, rapid, inexpensive and objective. [Copyright &y& Elsevier]

Abstract: The laminin tyrosine–isoleucine–glycine–serine–arginine (YIGSR) peptide, corresponding to the 929-933 sequence of β1 chain, is known to inhibit tumor growth and metastasis. In the present study, we observed that YIGSR not only inhibited the growth and migration of prostate cancer cells in a dose-dependent manner but also decreased mitochondrial membrane potential, inhibited ATP synthesis and increased caspase-9 activity. Investigation into the interaction of YIGSR with 67LR, the receptor for laminin and polyphenol (­) epigallocatechin-3-gallate (EGCG) employing MVD (Molegro Virtual Docker, an integrated platform for predicting protein ligand interactions), revealed that the binding site of YIGSR was the same as that of EGCG that explains as to why YIGSR is able to inhibit the cytotoxicity of EGCG against PC-3 cells. [Copyright &y& Elsevier]

Abstract: A novel experimental method was developed to study the origin of the voltammetric response of human prostate cancer (PC-3) cell suspension as a model in consideration of the biological characters of living cells. The presence of guanine and xanthine in the cell eluent secreted by the living cells was verified by HPLC assay with a DAD system and chemometric method. Comparative studies of voltammetric behaviors of the PC-3 cell suspension, the PC-3 cell eluent, and the PC-3 cell sediment re-suspension showed that the voltammetric response of the PC-3 cells was given by xanthine and guanine bases in the PC-3 cell eluent, not by the cells. Linear relationship between the peak currents of guanine and xanthine in the cell eluent and the cell concentrations was found. Other factors, such as the cell secretion time and the immersion time of the multiwalled carbon nanotubes modified glassy carbon electrode (MWCNTs-modified GCE) in the cell eluent, also influenced the intensity of the peak currents. The biochemical mechanisms of the voltammetric behavior for the cell suspension were proposed. [Copyright &y& Elsevier]

Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially prostate cancers. Some chemotherapeutic agents aimed to decrease ODC expression showed inhibitory effects on cancer cells. In this study, we examined the effect of adenoviral-transduced antisense ODC on prostate cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and LNCap. Expression of ODC and concentration of polyamines in cells were determined by Western blotting and HPLC. MTT (3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze the effect on cell growth. Cell cycle was evaluated by FCM and cellular invasion by Matrigel invasion assay. A nude mouse xenograft model was used to examine tumorigenicity. Expression of ODC in PC-3 and LNCap cells were reduced to 45 and 59%, and three polyamines were also decreased by the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and cell cycle arrested at G1 phase. Matrigel invasion assay showed relatively low invasion. Marked suppression of tumor formation was observed in the xenograft model. This study suggests that rAd-ODC/Ex3as has the antitumor effect on the human prostate cancer cells.Prostate Cancer and Prostatic Diseases (2005) 8, 280–286. doi:10.1038/sj.pcan.4500808; published online 16 August 2005 [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is a bone metastatic cancer and is the second leading cause of cancer-related death in men. Prolonged progression-free survival of prostate cancer patients is associated with high regucalcin expression in the tumor tissues. This study investigates the underlying mechanism by which regucalcin prevents bone metastatic activity of prostate cancer cells., Methods: Human prostate cancer PC-3 or DU-145 wild-type cells or regucalcin-overexpressing PC-3 or DU-145 cells (transfectants) were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum., Results: Overexpressed regucalcin suppressed the migration and invasion of bone metastatic human prostate cancer cells in vitro, and it reduced the levels of key proteins in metastasis including Ras, Akt, MAPK, RSK-2, mTOR, caveolin-1, and integrin β1. Invasion of prostate cancer cells was promoted by coculturing with preosteoblastic MC3T3-E1 or preosteoclastic RAW264.7 cells. Coculturing with cancer cells and bone cells repressed the growth of preosteoblastic cells and enhanced osteoclastogenesis of preosteoclastic cells, and these alterations were caused by a conditioned medium from cancer cell culture. Disordered differentiation of bone cells was prevented by regucalcin overexpression. Production of tumor necrosis factor-α (TNF-α) in cancer cells was blocked by overexpressed regucalcin. Of note, the effects of conditioned medium on bone cells were prevented by NF-κB inhibitor. TNF-α may be important as a mediator in the crosstalk between cancer cells and bone cells., Conclusion: Overexpression of regucalcin suppressed the migration, invasion, and bone metastatic activity of human prostate cancer cells. This study may provide a new strategy for therapy with the regucalcin gene transfer., (© 2022 Wiley Periodicals LLC.)

Prostate cancer (PCa) is addressed as the second most common form of onco-threat worldwide and is usually considered as the major cause of mortality in men. Recent times have seen a surge in exploration of plant-derived components for alternative therapeutical interventions against different oncological malignancies. Dammarolic acid or Asiatic acid (AsA) is an aglycone asiaticoside that has been reported for its efficacy in several ailments including cancer. The current study aimed to investigate the anti-proliferative potency of AsA against human prostate cancer PC-3 cells. Purified AsA was diluted and PC-3 cells were exposed to 20, 40, and 80 µM concentration and incubated for 24 h. Post-exposure, PC-3 cells showcased a substantial loss of their viability at 20 µM ( p < 0.05), moreover, this reduction in cell viability escalated proportionally with an increase in AsA at concentrations of 40 and 80 µM ( p < 0.01; p < 0.001) respectively. AsA-impelled loss of cellular viability was also evident from the acridine orange-stained photomicrographs, which was also used to quantify the viable and apoptotic cells using Image J software. Additionally, quantification of ROS within PC-3 cells also exhibited an increase in DCF-DA-mediated fluorescence intensity post-exposure to AsA in a dose-dependent manner. AsA-induced apoptosis in PC-3 cells was shown to be associated with augmented activity of caspase-3 proportionally to the AsA concentrations. Thus, initially, this exploratory study explicated that AsA treatment leads to anti-proliferative effects in PC-3 cells by enhancing oxidative stress and inciting apoptosis en route to onset of nuclear fragmentation.

• BaP enhances the proliferative and mutagenic activity in PC-3 cells. • BaP promotes G1 to S transition by upregulation of cyclinD1 and CDK4 in PC-3 cells. • E-cadherin, Slug, Snail, and JAK2-STAT3 pathway induction are involved in BaP effect on PC-3 cells. Environmental carcinogen benzo(a)pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons (PAHs). BaP is strongly associated with prostate carcinogenesis. However, the molecular mechanism of BaP in development of prostate carcinoma remains largely unknown. The aim of this study was to investigate the effect and mechanism of BaP on the development in prostate cancer. PC-3 cells were exposed to different concentrations of BaP for 24, 48, 72 h, respectively. We analyzed the effect of BaP on PC-3 cell viability, cell cycle, DNA strand breaks, mutagenic activity, and migration. The expression of associated regulatory genes and the effect of JAK2/STAT3 signaling were also measured to explore the relationships among BaP metabolism, the JAK2/STAT3 pathway and proliferative activity in PC-3 cells. We observed significant effects on proliferation, DNA strand breaks and mutagenic activity after BaP exposure in PC-3 cells, and inhibitors of CYP1 and the AhR transcription factor α -naphthoflavone (ANF) and CH223191 treatment clearly reduced both cell survival and mutagenesis associated with BaP exposure. Reduction in G0-G1 phase population and elevation in S phase were observed after BaP exposure. Migratory cells for PC-3 were significantly increased. The results were further confirmed by the expression of mRNA levels in the significant increments of Snail, Slug, MMP-9, CYP1A1, CYP1B1, CycilnD1, CDK4 and significant reduction of E-cadherin. Significant enhancements were found in the expression of JAK2, STAT3 after BaP treatment. Additionally, activator IL-6 significantly enhanced the effect of BaP on cell survival, mutagenic activity, Cyclin D1, CDK4, Snail, and JAK2/STAT3 expression in PC-3 cells. Significant reductions in cell survival, mutagenic activity, Cyclin D1, CDK4, Snail, and JAK2/STAT3 expression were found after inhibitor AG490, ANF and CHJ223191 treatment. These findings reveal that BaP enhances the proliferative and mutagenic activity via JAK2-STAT3 pathway in PC-3 cells, and provide the additional evidence to understand the crucial role of BaP in prostate cancer carcinogenesis. [ABSTRACT FROM AUTHOR]

• Beta-lapachone (β-Lap) was encapsulated in cyclodextrins, nanoparticles and liposomes. • Cyclodextrins and double loaded vesicles provided the best drug loading properties. • No β-Lap delivery system showed enhanced cytotoxicity compared to the free drug. • B-Lap demonstrated no cell selectivity based on interaction with enzyme NQO1. • Functionalization of β-Lap systems is required for safe application in cancer therapy. Beta-lapachone (β-Lap) is an anticancer drug activated by the NAD(P)H:quinone oxidoreductase (NQO1), an enzyme over-expressed in a large variety of tumors. B-Lap is poorly soluble in water and in most biocompatible solvents. Micellar systems, liposomes and cyclodextrins (CDs) have been proposed for its solubilization. In this work, we analyzed the properties and in vitro efficacy of β-Lap loaded in polymer nanoparticles, liposome bilayers, complexed with sulfobutyl-ether (SBE)- and hydroxypropyl (HP)-β cyclodextrins, or double loaded in phospholipid vesicles. Nanoparticles led to the lowest drug loading. Encapsulation of [β-Lap:CD] complexes in vesicles made it possible to slightly increase the encapsulation rate of the drug in liposomes, however at the cost of poor encapsulation efficiency. Cytotoxicity tests generally showed a higher sensitivity of NIH 3T3 and PNT2 cells to the treatment compared to PC-3 cells, but also a slight resistance at high β-Lap concentrations. None of the studied β-Lap delivery systems showed significant enhanced cytotoxicity against PC-3 cells compared to the free drug. Cyclodextrins and double loaded vesicles, however, appeared more efficient drug delivery systems than liposomes and nanoparticles, combining both good solubilizing and cytotoxic properties. Ligand-functionalized double loaded liposomes might allow overcoming the lack of selectivity of the drug. [ABSTRACT FROM AUTHOR]

Prostate cancer, which is a bone metastatic cancer, is the second leading cause of cancer-related death in men. There is no effective treatment for metastatic prostate cancer. Regucalcin has been shown to contribute as a suppressor in various types of human cancers. In the present study, furthermore, we investigate an involvement of regucalcin in suppression of prostate cancer. Regucalcin expression was compared in 131 primary tumor tissues and 19 metastatic tumor tissues in prostate cancer patients. Regucalcin expression in the metastatic tumor was found to be reduced as compared with that in primary tumor. The progression-free survival rate was prolonged in patients with a higher regucalcin expression. Translationally, overexpression of regucalcin in bone metastatic human prostate cancer PC-3 and DU-145 cells suppressed colony formation and cell growth in vitro. Mechanistically, overexpressed regucalcin enhanced the levels of p53, Rb, and p21, and decreased the levels of Ras, PI3 kinase, Akt, and mitogen-activated protein kinase, leading to suppression of cell growth. Furthermore, higher regucalcin expression suppressed the levels of nuclear factor-κB p65, β-catenin, and signal transducer and activator of transcription 3, which regulate a transcription activity. Cell growth was promoted by culturing with the calcium agonist Bay K 8644. This effect was blocked by overexpression of regucalcin. Notably, overexpressed regucalcin suppressed bone metastatic activity of PC-3 and DU-145 cells when cocultured with preosteoblastic or preosteoclastic cells. Regucalcin may suppress the development of human prostate cancer, suggesting that gene delivery systems in which its expression is forced may be a novel therapeutic strategy., 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 © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To observe the effects of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the proliferation, migration and invasive ability of prostate cancer PC-3 cells in vitro and explore the underlying mechanisms., Methods: We cultured prostate cancer PC-3 cells in vitro and treated them with 3-BrPA at different concentrations for 24, 48 and 72 hours. Then we observed the morphological changes of the PC-3 cells under the inverted microscope. We also detected the effects of different concentrations of 3-BrPA on the proliferation, migration and invasive ability of the cells by MTT, wound-scratch and Transwell assays and determined the protein expressions of glucose transporter-1 (GLUT1), matrix metalloproteinase-14 (MMP-14), MMP-9 and MMP-2 in the PC-3 cells by Western blot., Results: More significant changes were observed in the morphology of the PC-3 cells with increased concentrations of 3-BrPA. MTT assay showed that the inhibition rate of the proliferation of the PC-3 cells was remarkably increased in a concentration- and time-dependent manner (P<0.01). Wound-scratch and Transwell assays exhibited significant decreases in the scratch healing rate and number of invasive cells after 24 hours of intervention with 3-BrPA at 25, 50 and 100 μmol/L, even more significant after treated for 48 hours at the concentrations of 50 and 100 μmol/L (P<0.01). The expressions of the GLUT1, MMP-14, MMP-9 and MMP-2 proteins were markedly down-regulated after 3-BrPA intervention in comparison with those in the control group (P<0.01)., Conclusions: The glycolysis inhibitor 3-BrPA reduces the proliferation, migration and invasive ability of prostate cancer PC-3 cells by down-regulating the expressions of the related proteins GLUT1, MMP-14, MMP-9 and MMP-2.

Objective: To investigate the effect of small interfering RNA silencing the vitamin D receptor (VDR) on the biological behavior of prostate cancer PC-3 cells., Methods: We constructed the VDR-shRNA lentiviral vector and determined the mRNA and protein expressions of VDR by RT-PCR and Western blot. Using scratch wound healing and Transwell chamber assays, we detected the changes in the migration and invasiveness of the PC-3 cells after silencing VDR., Results: The VDR-shRNA plasmid significantly interfered the VDR expression and successfully screened the cell lines with stable VDR-shRNA interference. The rate of scratch wound healing was markedly lower in the VDR interference group than in the blank control and LV3 negative control groups (59% vs 73.6% and 77.8%, P <0.05), but with no statistically significant difference between the latter two (P >0.05), and so was the count of permeable cells (P <0.05), but with no significant difference between the latter two groups, either (P >0.05). The migration ability and invasiveness of the VDR-treated cells were remarkably decreased as compared with those of the control cells., Conclusions: Down-regulated expression of the VDR gene may reduce the migration and invasiveness of prostate cancer cells.

Prostate cancer stem-like cells (PCSLCs) are considered to be the 'seed' of prostate cancer. The aim of this study was to confirm that the PC-3 cells, which we isolated and enriched from PC-3 cells through magnetic bead cell sorting (MACS) and serum-free medium (SFM) culture, were PCSLCs. Combinations of MACS, flow cytometry (FCM), SFM and immunocytochemistry (ICC) were used to ensure the positive expression of CD133 and CD44 on PC-3 and sphere-forming cell membranes. Self-renewal, multi-potential differentiation, unlimited proliferation and permanency assays were also applied to indentify whether the PC-3 cells exhibited the characteristics of cancer stem cells (CSCs). As a result, there was a low proportion of PCSLCs in the PC-3 cells. In the FCM assay, the proportion of cells expressing CD133 or CD44 in the PC-3 cells was 0.51 and 0.31%, respectively. In addition, we found that the proportion of PC-3 cells sorted by MACS that expressed CD133 was significantly increased compared with that of the sphere-forming cells cultured in SFM (99.09 vs. 84.80%, P<0.05), while no difference was observed in the proportion of cells expressing CD44 between them (99.88 vs. 99.82%, P>0.05). The expression of PAP and AR as detected by western blot analysis of induced PCSLCs was significantly increased compared with that of uninduced PCSLCs (P<0.05); the proliferation capacity of PCSLCs was significantly higher than that of both the PC-3 cells (P<0.05) and induced PCSLCs (P<0.05). Furthermore, the PCSLCs that were isolated from SFM and MACS both demonstrated certain characteristics of stem cells and should be considered as stem cell-like. These data may hold potential for further exploring the role of PCSLCs.