A self-assembled π-conjugated system as an anti-proliferative agent in prostate cancer cells and a probe for intra-cellular imaging

RSC Advances ◽  
2014 ◽  
Vol 4 (89) ◽  
pp. 48433-48437 ◽  
Author(s):  
Krishnamoorthy Lalitha ◽  
Preethi Jenifer ◽  
Y. Siva Prasad ◽  
Kumarasamy Muthusamy ◽  
George John ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Renewable Resource ◽  
Cellular Imaging ◽  
Prostate Cancer Cells ◽  
Conjugated Systems ◽  
Pc3 Cells ◽  
Self Assembled

Herein, self-assembled π-conjugated systems derived from renewable resource are reported as a probe for intra-cellular imaging and an anti-proliferative agent for PC3 cells.

scholarly journals Cytostatic Action of Novel Histone Deacetylase Inhibitors in Androgen Receptor-Null Prostate Cancer Cells

2021 ◽  
Vol 14 (2) ◽  
pp. 103
Author(s):  
Zohaib Rana ◽  
Joel D. A. Tyndall ◽  
Muhammad Hanif ◽  
Christian G. Hartinger ◽  
Rhonda J. Rosengren
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Hdac Inhibitors ◽  
G1 Arrest ◽  
Prostate Cancer Cells ◽  
Prostate Tumors ◽  
Normal Prostate ◽  
Pc3 Cells ◽  
Du145 Cells

Androgen receptor (AR)-null prostate tumors have been observed in 11–24% of patients. Histone deacetylases (HDACs) are overexpressed in prostate tumors. Therefore, HDAC inhibitors (Jazz90 and Jazz167) were examined in AR-null prostate cancer cell lines (PC3 and DU145). Both Jazz90 and Jazz167 inhibited the growth of PC3 and DU145 cells. Jazz90 and Jazz167 were more active in PC3 cells and DU145 cells in comparison to normal prostate cells (PNT1A) and showed a 2.45- and 1.30-fold selectivity and higher cytotoxicity toward DU145 cells, respectively. Jazz90 and Jazz167 reduced HDAC activity by ~60% at 50 nM in PC3 lysates. At 4 μM, Jazz90 and Jazz167 increased acetylation in PC3 cells by 6- to 8-fold. Flow cytometry studies on the cell phase distribution demonstrated that Jazz90 causes a G0/G1 arrest in AR-null cells, whereas Jazz167 leads to a G0/G1 arrest in DU145 cells. However, apoptosis only occurred at a maximum of 7% of the total cell population following compound treatments in PC3 and DU145 cells. There was a reduction in cyclin D1 and no significant changes in bcl-2 in DU145 and PC3 cells. Overall, the results showed that Jazz90 and Jazz167 function as cytostatic HDAC inhibitors in AR-null prostate cancer cells.

scholarly journals Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Zongliang Lu ◽  
Wei Song ◽  
Yaowen Zhang ◽  
Changpeng Wu ◽  
Mingxing Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Castration Resistance ◽  
Prostate Cancer Cells ◽  
Antitumor Effects ◽  
Platycodin D ◽  
Downstream Target ◽  
Anti Cancer ◽  
Pc3 Cells ◽  
Androgen Independent

Castration-resistant (androgen-independent) and PTEN-deficient prostate cancer is a challenge in clinical practice. Sorafenib has been recommended for the treatment of this type of cancer, but is associated with several adverse effects. Platycodin D (PD) is a triterpene saponin with demonstrated anti-cancer effects and a good safety profile. Previous studies have indicated that PC3 cells (PTEN -/-, AR -/-) are sensitive to PD, suggesting that it may also be a useful treatment for castration-resistance prostate cancer. We herein investigated the effects of combining PD with sorafenib to treat PTEN-deficient prostate cancer cells. Our data show that PD promotes sorafenib-induced apoptosis and cell cycle arrest in PC3 cells. Of interest, PD only promoted the anti-cancer effects of sorafenib in Akt-positive and PTEN-negative prostate cancer cells. Mechanistic studies revealed that PD promoted p-Akt ubiquitination by increasing the p-Akt level. PD also increased the protein and mRNA expression of FOXO3a, the downstream target of Akt. Meanwhile, PD promoted the activity of FOXO3a and increased the protein expression of Fasl, Bim and TRAIL. Interestingly, when FOXO3a expression was inhibited, the antitumor effects of both PD and sorafenib were individually inhibited, and the more potent effects of the combination treatment were inhibited. Thus, the combination of PD and sorafenib may exert potent anti-cancer effects specifically via FOXO3a. The use of Akt inhibitors or FOXO3a agonists, such as PD, may represent a promising approach for the treatment of androgen-independent and PTEN-deficient prostate cancer.

scholarly journals ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro

2020 ◽  
Vol 19 ◽  
pp. 153303382094806
Author(s):  
Guangxing Tan ◽  
Lin Jiang ◽  
Gangqin Li ◽  
Kuan Bai
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Nude Mouse ◽  
Luciferase Reporter ◽  
Control Group ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Mouse Xenograft Model ◽  
Pc3 Cells ◽  
Du145 Cells

Objective: To explore the effect and the related mechanism of STAT3 inhibitor AG-490 on inhibiting the proliferation of prostate cancer cells. Methods: PC3 cells and DU145 cells were cultured stably and treated with AG-490 to detect the changes in the activity of PC3 cells and DU145 cells. Thirty 6-8 weeks male BALB/c nude mouse were randomly divided into a control group, a DMSO group, and an AG-490 group to detect differences in various indexes . Results: The overexpression of miR-503-5p depends on the activation of STAT3. After treatment with AG-490, The proliferation and invasion of PC3 cells and DU145 cells and the expression of miR-503-5p were all reduced. Luciferase reporter assay demonstrated that the target proteins of miR-503-5p include PDCD4, TIMP-3, and PTEN. After treatment with AG-490, the expression of PDCD4, TIMP-3, and PTEN in cells was significantly up-regulated. IL-6-induced overexpression of miR-503-5p and restored the expression of STAT3, demonstrating the correlation between STAT3 and miR-503-5p. AG-490 can inhibit tumor growth and induce tumor cell apoptosis in the PC3 BALB/c nude mouse xenograft model. Western blotting and immunohistochemical staining showed that the expression levels of STAT3, Ki67, Bcl-2 and MMP-2 in the AG-490 group were significantly reduced, and the expression of PDCD4, TIMP-3 and PTEN increased. Conclusion: AG-490 can inhibit the growth of prostate cancer cells in a miR-503-5p-dependent manner by targeting STAT3. AG-490 is expected to become a new candidate drug for the treatment of prostate cancer.

Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in Human Prostate Cancer Cells

2018 ◽  
Vol 46 (07) ◽  
pp. 1625-1643 ◽  
Author(s):  
Hung-En Chen ◽  
Ji-Fan Lin ◽  
Te-Fu Tsai ◽  
Yi-Chia Lin ◽  
Kuang-Yu Chou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Allyl Isothiocyanate ◽  
Beclin 1 ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Normal Prostate ◽  
Autophagy Induction ◽  
Pc3 Cells

Allyl isothiocyanate (AITC), one of the most widely studied phytochemicals, inhibits the survival of human prostate cancer cells while minimally affecting normal prostate epithelial cells. Our study demonstrates the mechanism of AITC-induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and PC3 cells, judging from the increased level of LC3-II protein in a dose- and time-dependent manner, but not in the normal prostate epithelial cell (PrEC). Inhibition of autophagy in AITC-treated cells decreased cell viability and enhanced apoptosis, suggesting that the autophagy played a protective role. There are several pathways activated in ATIC-treated cells. We detected the phosphorylation forms of mTOR, ERK, AMPK, JNK and p38, and ERK AMPK and JNK activation were also detected. However, inhibition of AITC-activated ERK, AMPK and JNK by pre-treatment of specific inhibitors did not alter autophagy induction. Finally, increased beclin-1 expression was detected in AITC-treated cells, and inhibition of AITC-induced beclin-1 attanuated autophagy induction, indicating that AITC-induced autophagy occurs through upregulating beclin-1. Overall, our data show for the first time that AITC induces protective autophagy in Rv1 and PC3 cells through upregulation of beclin-1. Our results could potentially contribute to a therapeutic application of AITC in prostate cancer patients.

scholarly journals TGF-β Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1768-1779 ◽  
Author(s):  
BaoHan T. Vo ◽  
Derrick Morton ◽  
Shravan Komaragiri ◽  
Ana C. Millena ◽  
Chelesie Leath ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Protein Levels ◽  
Prostate Cells ◽  
Pc3 Cells ◽  
Cox 2

Abstract TGF-β plays an important role in the progression of prostate cancer. It exhibits both tumor suppressor and tumor-promoting activities. Correlations between cyclooxygenase (COX)-2 overexpression and enhanced production of prostaglandin (PG)E2 have been implicated in cancer progression; however, there are no studies indicating that TGF-β effects in prostate cancer cells involve PGE2 synthesis. In this study, we investigated TGF-β regulation of COX-1 and COX-2 expression in prostate cancer cells and whether the effects of TGF-β on cell proliferation and migration are mediated by PGE2. COX-1 protein was ubiquitously expressed in prostate cells; however, COX-2 protein levels were detected only in prostate cancer cells. TGF-β treatment increased COX-2 protein levels and PGE2 secretion in PC3 cells. Exogenous PGE2 and PGF2α had no effects on cell proliferation in LNCaP, DU145, and PC3 cells whereas PGE2 and TGF-β induced migration and invasive behavior in PC3 cells. Only EP2 and EP4 receptors were detected at mRNA levels in prostate cells. The EP4-targeting small interfering RNA inhibited PGE2 and TGF-β-induced migration of PC3 cells. TGF-β and PGE2 induce activation of PI3K/AKT/mammalian target of rapamycin pathway as indicated by increased AKT, p70S6K, and S6 phosphorylation. Rapamycin completely blocked the effects of TGF-β and PGE2 on phosphorylation of p70S6K and S6 but not on AKT phosphorylation. PGE2 and TGF-β induced phosphorylation of AKT, which was blocked by antagonists of PGE2 (EP4) receptors (L161982, AH23848) and PI3K inhibitor (LY294002) in PC3 cells. Pretreatment with L161982 or AH23848 blocked the stimulatory effects of PGE2 and TGF-β on cell migration, whereas LY294002 or rapamycin completely eliminated PGE2, TGF-β, and epidermal growth factor-induced migration in PC3 cells. We conclude that TGF-β increases COX-2 levels and PGE2 secretion in prostate cancer cells which, in turn, mediate TGF-β effects on cell migration and invasion through the activation of PI3K/AKT/mammalian target of rapamycin pathway.

scholarly journals The Impact of Ang-(1-9) and Ang-(3-7) on the Biological Properties of Prostate Cancer Cells by Modulation of Inflammatory and Steroidogenesis Pathway Genes

2020 ◽  
Vol 21 (17) ◽  
pp. 6227
Author(s):  
Kamila Domińska ◽  
Karolina Kowalska ◽  
Kinga Anna Urbanek ◽  
Dominika Ewa Habrowska-Górczyńska ◽  
Tomasz Ochędalski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Renin Angiotensin System ◽  
Biological Properties ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
M Cell ◽  
Pc3 Cells ◽  
The Impact

The local renin–angiotensin system (RAS) plays an important role in the pathophysiology of the prostate, including cancer development and progression. The Ang-(1-9) and Ang-(3-7) are the less known active peptides of RAS. This study examines the influence of these two peptide hormones on the metabolic activity, proliferation and migration of prostate cancer cells. Significant changes in MTT dye reduction were observed depending on the type of angiotensin and its concentration as well as time of incubation. Ang-(1-9) did not regulate the 2D cell division of either prostate cancer lines however, it reduced the size of LNCaP colonies formed in soft agar, maybe through down-regulation of the HIF1a gene. Ang-(3-7) increased the number of PC3 cells in the S phase and improved anchorage-independent growth as well as mobility. In this case, a significant increase in MKI67, BIRC5, and CDH-1 gene expression was also observed as well as all members of the NF-kB family. Furthermore, we speculate that this peptide can repress the proliferation of LNCaP cells by NOS3-mediated G2/M cell cycle arrest. No changes in expression of BIRC5 and BCL2/BAX ratio were observed but a decrease mRNA proapoptotic BAD gene was seen. In the both lines, Ang-(3-7) improved ROCK1 gene expression however, increased VEGF and NOS3 mRNA was only seen in the PC3 or LNCaP cells, respectively. Interestingly, it appears that Ang-(1-9) and Ang-(3-7) can modulate the level of steroidogenic enzymes responsible for converting cholesterol to testosterone in both prostate cancer lines. Furthermore, in PC3 cells, Ang-(1-9) upregulated AR expression while Ang-(3-7) upregulated the expression of both estrogen receptor genes. Ang-(1-9) and Ang-(3-7) can impact on biological properties of prostate cancer cells by modulating inflammatory and steroidogenesis pathway genes, among others.

scholarly journals Effects of the Antiandrogen Flutamide on the Expression of Protein Kinase C Isoenzymes in LNCaP and PC3 Human Prostate Cancer Cells

2004 ◽  
Vol 24 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Leire Montalvo ◽  
María J. Carmena ◽  
Oscar Bolaños ◽  
Nieves Rodríguez-Henche ◽  
Manuel Sánchez-Chapado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Cultured Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Kinase C ◽  
Pc3 Cells

Flutamide is a nonsteroidal antiandrogen that is frequently used for total androgen blockage in the treatment of advanced prostate cancer. We investigated the effect of this antiandrogen on the expression of protein kinase C (PKC) isoenzymes (α, β1, ∊, ζ) that are involved in cell growth, apoptosis and neoplastic transformation. Androgen-dependent (LNCaP) and independent (PC3) human prostate cancer cells were cultured in a medium that contained fetal bovine serum (FBS) or charcoal-stripped serum (CSS) and treated with 10 μM flutamide. The expression of PKC isoenzymes and the androgen receptor (AR) were analyzed by Western blot and RT-PCR, respectively. Serum steroids differentially regulate the expression of PKC isoenzymes in LNCaP and PC3 cells. Flutamide up-regulated the expression of α, β1 and ζ, but not ∊, PKC isoenzymes in CSS-LNCaP cells. These results were not homogeneously reproduced in the presence of androgens. We observed an opposite effect of flutamide, compared to CSS, on PKCβ1 isoform expression in CSS-LNCaP suggesting that this antiandrogen exerts an agonistic effect. In PC3 cells flutamide potentiated the expression of the four PKC isoenzymes in almost all conditions tested (FBS- and CSS-cultured cells). Such effect of flutamide in PC3 cells is independent of AR since no expression of AR was detected. These results provide new evidence on antagonistic/agonistic responses of prostate cancer cells to antiandrogen drugs that are widely used in therapy and show that flutamide can elicit responses in prostate cancer cells that do not express AR.

scholarly journals Down-regulation of F-actin and paxillin by N-(3-(1Htetrazol- 1-yl)phenyl) isonicotinamide derivative inhibits proliferation of prostate cancer cells

2020 ◽  
Vol 19 (7) ◽  
pp. 1389-1395
Author(s):  
Liang Wei ◽  
Ying Mu ◽  
Lina Ji ◽  
Xin Guo ◽  
Tongyi Li
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Cell Counting ◽  
Prostate Cancer Cells ◽  
Caspase 9 ◽  
Keywords Prostate Cancer ◽  
Keywords Prostate ◽  
Pc3 Cells

Purpose: To investigate the effect of N-(3-(1H-tetrazol-1-yl)phenyl) isonicotinamide derivative (TPIN) on prostate cancer cells, and the mechanism involved.Methods: The cytotoxicity of TPIN in DU145 and PC3 cells was determined using Cell Counting Kit-8, while apoptosis induction was assayed by flow cytometry using Annexin V-fluorescein isothiocyanate dye. Changes in expressions of F-actin, RAC-α and paxillin were determined by western blot assay.Results: Cell proliferation was effectively inhibited by TPIN in the concentration range of 0.75-15 μM. The values of half-minimum inhibitory concentration (IC50) of TPIN for DU145 and PC3 cells at 48 h were 5.6 and 10.2 μM, respectively (p < 0.05). Treatment with 5.6 μM TPIN increased apoptosis to 59.64 % in DU145 cells, and 54.21% in PC3 cells. Cleaved caspase-3 and caspase-9 levels were increased by TPIN treatment in both cell lines (p < 0.05). Moreover, the levels of F-actin and paxillin were significantly downregulated by TPIN treatment in DU145 and PC3 cells (p < 0.05). In TPIN-treated DU145 and PC3 cells, cofilin-1expression was up-regulated, relative to control cells.Conclusion: TPIN exhibits cytotoxic effect on prostate cancer cells via activation of apoptosis. It elevates cofilin-1 and the expressions of targets F-actin and paxillin in prostate cancer cells. Thus, TPIN is a potential chemotherapeutic agent for prostate cancer. However, further investigations, including clinical trials are required to authenticate these findings. Keywords: Prostate cancer, F-actin, Paxillin, Apoptosis, Caspases

scholarly journals Bcl-xL Is Overexpressed in Hormone-Resistant Prostate Cancer and Promotes Survival of LNCaP Cells via Interaction with Proapoptotic Bak

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4960-4967 ◽  
Author(s):  
Carolina Castilla ◽  
Belén Congregado ◽  
David Chinchón ◽  
Francisco J. Torrubia ◽  
Miguel A. Japón ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Topoisomerase I ◽  
Immunohistochemical Analysis ◽  
Gleason Grade ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Pc3 Cells ◽  
Prostate Carcinomas

Androgen-sensitive prostate cancer cells turn androgen resistant through complex mechanisms that involve dysregulation of apoptosis. We investigated the role of antiapoptotic Bcl-xL in the progression of prostate cancer as well as the interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and -independent prostate cancer cells. Immunohistochemical analysis was used to study the expression of Bcl-xL in a series of 139 prostate carcinomas and its association with Gleason grade and time to hormone resistance. Expression of Bcl-xL was more abundant in prostate carcinomas of higher Gleason grades and significantly associated with the onset of hormone-refractory disease. In vivo interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h, Bcl-xL decreased gradually and Bak increased coincidentally with the progress of apoptosis. These results support a model in which Bcl-xL would exert an inhibitory effect over Bak via heterodimerization. We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer.

scholarly journals Zoledronic Acid Elicits Proinflammatory Cytokine Profile in Osteolytic Prostate Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Chia Lin ◽  
Po-Cheng Liao ◽  
Te-Fu Tsai ◽  
Kuang-Yu Chou ◽  
Hung-En Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Prostate Cancer Cell ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Low Concentrations ◽  
Pc3 Cells ◽  
Inflammatory Profile

Zoledronic acid (ZA), a bisphosphonate used to prevent skeletal fractures in patients with cancers, was demonstrated to induce apoptosis in a number of cancer cells. Our previous study showed that ZA also induces autophagic cell death in metastatic prostate cancer cells. However, the clinical trials using ZA in the treatment of metastatic prostate cancer did not have a longer diseases-free period. Since most of ZA was attracted to the bone after administration, we hypothesized that local prostate cancer cells may evolve prosurvival pathways upon low concentration of ZA treatment. In this study, we investigated the inflammatory effects of ZA on osteolytic PC3 prostate cancer cell, since inflammation was reported to be related to cancer development and survival. Exposure of PC3 cells to various concentrations of ZA resulted in induction of apoptosis and autophagy. The expression of inflammatory biomarkers including interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), and NF-κB was remarkably upregulated in response to ZA treatment in a dose- and time-dependent manner. The production of IL-6 was elevated upon ZA treatment. The antiapoptotic protein Bcl2 was increased with parallel increased level of IL-6. Our data suggest that treatment with low concentrations of ZA enhances the inflammatory profile and may serve as a prosurvival signaling pathway in PC3 cells.

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